NF-κB in cancer therapy

The transcription factor nuclear factor kappa B (NF-κB) has attracted increasing attention in the field of cancer research from last few decades. Aberrant activation of this transcription factor is frequently encountered in a variety of solid tumors and hematological malignancies. NF-κB family members and their regulated genes have been linked to malignant transformation, tumor cell proliferation, survival, angiogenesis, invasion/metastasis, and therapeutic resistance. In this review, we highlight the diverse molecular mechanism(s) by which the NF-κB pathway is constitutively activated in different types of human cancers, and the potential role of various oncogenic genes regulated by this transcription factor  in cancer development and progression. Additionally, various pharmacological approaches employed to target the deregulated NF-κB signaling pathway, and their possible therapeutic potential in cancer therapy is also discussed briefly.

[1]  Pingfu Fu,et al.  Nuclear factor-kappaB/p65 (Rel A) is constitutively activated in human prostate adenocarcinoma and correlates with disease progression. , 2004, Neoplasia.

[2]  P. Tak,et al.  UvA-DARE (Digital Academic Repository) NF-kappa B: a key role in inflammatory diseases , 2000 .

[3]  T. Maniatis,et al.  Transcriptional regulation of endothelial cell adhesion molecules : NF-icB and cytokine-inducible enhancers , 2004 .

[4]  P. Elliott,et al.  Enhancement of radiosensitivity by proteasome inhibition: implications for a role of NF-kappaB. , 2001, International journal of radiation oncology, biology, physics.

[5]  J. Gutkind,et al.  Dysregulated molecular networks in head and neck carcinogenesis. , 2009, Oral oncology.

[6]  G. Clayman,et al.  Antisense inhibition of cyclin D1 in human head and neck squamous cell carcinoma. , 2000, Archives of otolaryngology--head & neck surgery.

[7]  A. E. Rogers,et al.  Aberrant nuclear factor-kappaB/Rel expression and the pathogenesis of breast cancer. , 1997, The Journal of clinical investigation.

[8]  Akt-dependent regulation of NF-{kappa}B is controlled by mTOR and Raptor in association with IKK. , 2008, Genes & development.

[9]  W. Funkhouser,et al.  Selective activation of NF-κB subunits in human breast cancer: potential roles for NF-κB2/p52 and for Bcl-3 , 2000, Oncogene.

[10]  Christian Schmidt,et al.  NF-κB and AP-1 Connection: Mechanism of NF-κB-Dependent Regulation of AP-1 Activity , 2004, Molecular and Cellular Biology.

[11]  M. Arsura,et al.  Nuclear factor-kappaB and liver carcinogenesis. , 2005, Cancer letters.

[12]  S. Thorgeirsson,et al.  Transient activation of NF-κB through a TAK1/IKK kinase pathway by TGF-β1 inhibits AP-1/SMAD signaling and apoptosis: implications in liver tumor formation , 2003, Oncogene.

[13]  Katerina Akassoglou,et al.  NF-κB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1α , 2008, Nature.

[14]  R. Garavito,et al.  Cyclooxygenases: structural, cellular, and molecular biology. , 2000, Annual review of biochemistry.

[15]  R. DuBois,et al.  Cyclooxygenase Regulates Angiogenesis Induced by Colon Cancer Cells , 1998, Cell.

[16]  W. Isaacs,et al.  Cyclooxygenases in cancer: progress and perspective. , 2004, Cancer letters.

[17]  Y. Doki,et al.  Antisense to cyclin D1 inhibits the growth and tumorigenicity of human colon cancer cells. , 1997, Cancer research.

[18]  P. Tofilon,et al.  Preferential enhancement of tumor radioresponse by a cyclooxygenase-2 inhibitor. , 2000, Cancer research.

[19]  M. Czaja,et al.  NF‐κB inhibition sensitizes hepatocytes to TNF‐induced apoptosis through a sustained activation of JNK and c‐Jun , 2002, Hepatology.

[20]  L. Staudt Oncogenic activation of NF-kappaB. , 2010, Cold Spring Harbor perspectives in biology.

[21]  L. Howells,et al.  Inhibition of cyclo-oxygenase 2 expression in colon cells by the chemopreventive agent curcumin involves inhibition of NF-κB activation via the NIK/IKK signalling complex , 1999, Oncogene.

[22]  N. Perkins,et al.  Integrating cell-signalling pathways with NF-κB and IKK function , 2007, Nature Reviews Molecular Cell Biology.

[23]  J. Schmid,et al.  BMS-345541 Targets Inhibitor of κB Kinase and Induces Apoptosis in Melanoma: Involvement of Nuclear Factor κB and Mitochondria Pathways , 2006, Clinical Cancer Research.

[24]  Masao Tanaka,et al.  Increased nuclear factor-kB activation in human colorectal carcinoma and its correlation with tumor progression. , 2004, Anticancer research.

[25]  J. Romashkova,et al.  NF-kappaB is a target of AKT in anti-apoptotic PDGF signalling. , 1999, Nature.

[26]  M. Korc,et al.  Inhibition of cyclin D1 expression in human pancreatic cancer cells is associated with increased chemosensitivity and decreased expression of multiple chemoresistance genes. , 1999, Cancer research.

[27]  M. Widschwendter,et al.  Osteoclast differentiation factor RANKL controls development of progestin-driven mammary cancer , 2010, Nature.

[28]  S. Thorgeirsson,et al.  Role of the IκB Kinase Complex in Oncogenic Ras- and Raf-Mediated Transformation of Rat Liver Epithelial Cells , 2000, Molecular and Cellular Biology.

[29]  B. Aggarwal,et al.  Nuclear factor-kappaB: the enemy within. , 2004, Cancer cell.

[30]  K. Nakashiro,et al.  Overexpression of cyclooxygenase-2 is associated with radioresistance in oral squamous cell carcinoma. , 2004, Oral oncology.

[31]  R. Gaynor,et al.  Enhanced Chemosensitivity to Irinotecan by RNA Interference-Mediated Down-Regulation of the Nuclear Factor-κB p65 Subunit , 2004, Clinical Cancer Research.

[32]  David F. Kashatus,et al.  The Nuclear Factor κB Subunits RelA/p65 and c-Rel Potentiate but Are Not Required for Ras-Induced Cellular Transformation , 2004, Cancer Research.

[33]  E. Hurt,et al.  The role of IL-6 and STAT3 in inflammation and cancer. , 2005, European journal of cancer.

[34]  N. Perkins Achieving transcriptional specificity with nf-κb , 1997 .

[35]  A. Baldwin,et al.  Distinct mechanisms for regulation of the interleukin-8 gene involve synergism and cooperativity between C/EBP and NF-kappa B , 1993, Molecular and cellular biology.

[36]  Vinay Tergaonkar,et al.  Roles of NF-kappaB in health and disease: mechanisms and therapeutic potential. , 2009, Clinical science.

[37]  C. Sherr Cancer Cell Cycles , 1996, Science.

[38]  E. Wagner,et al.  Signal integration by JNK and p38 MAPK pathways in cancer development , 2009, Nature Reviews Cancer.

[39]  M. Karin,et al.  Inhibition of JNK activation through NF-κB target genes , 2001, Nature.

[40]  Michael Karin,et al.  Inflammation and colon cancer. , 2010, Gastroenterology.

[41]  J. Ruland,et al.  Aberrant NF-kappaB signaling in lymphoma: mechanisms, consequences, and therapeutic implications. , 2007, Blood.

[42]  L. Neckers,et al.  IL‐1β mediated up‐regulation of HIF‐lα via an NFkB/COX‐2 pathway identifies HIF‐1 as a critical link between inflammation and oncogenesis , 2003 .

[43]  D. Melisi,et al.  NF-kappa B as a target for cancer therapy. , 2007, Expert opinion on therapeutic targets.

[44]  H. Nakayama,et al.  High expression levels of nuclear factor kappaB, IkappaB kinase alpha and Akt kinase in squamous cell carcinoma of the oral cavity. , 2001, Cancer.

[45]  B. Aggarwal,et al.  Nuclear factor-kappaB: its role in health and disease. , 2004, Journal of molecular medicine.

[46]  C. Bucana,et al.  Blockade of NF-κB activity in human prostate cancer cells is associated with suppression of angiogenesis, invasion, and metastasis , 2001, Oncogene.

[47]  R. Gaynor,et al.  The anti-inflammatory agents aspirin and salicylate inhibit the activity of IκB kinase-β , 1998, Nature.

[48]  M. Resnick,et al.  Constitutive activation of PI3K‐Akt and NF‐κB during prostate cancer progression in autochthonous transgenic mouse model , 2005, The Prostate.

[49]  N. Mackman,et al.  LPS induction of gene expression in human monocytes. , 2001, Cellular signalling.

[50]  L. Lessard,et al.  Expression of NF‐κB in prostate cancer lymph node metastases , 2004 .

[51]  J C Reed,et al.  IAP family proteins--suppressors of apoptosis. , 1999, Genes & development.

[52]  G. Sledge,et al.  Constitutive activation of NF-kappaB during progression of breast cancer to hormone-independent growth , 1997, Molecular and cellular biology.

[53]  C. Sheehan,et al.  Expression of nuclear factor-kappa B and I kappa B alpha proteins in prostatic adenocarcinomas: correlation of nuclear factor-kappa B immunoreactivity with disease recurrence. , 2004, Clinical cancer research : an official journal of the American Association for Cancer Research.

[54]  A. Mishra,et al.  Curcumin induces stress response, neurite outgrowth and prevent nf-κb activation by inhibiting the proteasome function , 2009, Neurotoxicity Research.

[55]  Zhiwei Wang,et al.  NF-κB Signaling Pathway and Its Therapeutic Implications in Human Diseases , 2008, International reviews of immunology.

[56]  G. Sethi,et al.  Multifaceted link between cancer and inflammation. , 2012, Bioscience reports.

[57]  Jay Friedman,et al.  Current and potential inflammation targeted therapies in head and neck cancer. , 2009, Current opinion in pharmacology.

[58]  P. Tak,et al.  NF-κB: a key role in inflammatory diseases , 2001 .

[59]  M. Hung,et al.  HER-2/neu Blocks Tumor Necrosis Factor-induced Apoptosis via the Akt/NF-κB Pathway* , 2000, The Journal of Biological Chemistry.

[60]  E. Fosslien Biochemistry of Cyclooxygenase (COX)-2 Inhibitors and Molecular Pathology of COX-2 in Neoplasia , 2000, Critical reviews in clinical laboratory sciences.

[61]  N. Munshi,et al.  NF-kappa B as a therapeutic target in multiple myeloma. , 2002, The Journal of biological chemistry.

[62]  F. Lang,et al.  Enhancement of intrinsic tumor cell radiosensitivity induced by a selective cyclooxygenase-2 inhibitor. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[63]  E. Liu,et al.  Molecular profiling of transformed and metastatic murine squamous carcinoma cells by differential display and cDNA microarray reveals altered expression of multiple genes related to growth, apoptosis, angiogenesis, and the NF-kappaB signal pathway. , 2001, Cancer research.

[64]  Michael Karin,et al.  Reactive Oxygen Species Promote TNFα-Induced Death and Sustained JNK Activation by Inhibiting MAP Kinase Phosphatases , 2005, Cell.

[65]  Richard Pazdur,et al.  Velcade: U.S. FDA approval for the treatment of multiple myeloma progressing on prior therapy. , 2003, The oncologist.

[66]  C. Waes Nuclear Factor-κB in Development, Prevention, and Therapy of Cancer , 2007 .

[67]  Marty W. Mayo,et al.  Akt Stimulates the Transactivation Potential of the RelA/p65 Subunit of NF-κB through Utilization of the IκB Kinase and Activation of the Mitogen-activated Protein Kinase p38* , 2001, The Journal of Biological Chemistry.

[68]  K. McIntyre,et al.  BMS-345541 is a highly selective inhibitor of I kappa B kinase that binds at an allosteric site of the enzyme and blocks NF-kappa B-dependent transcription in mice. , 2003, The Journal of biological chemistry.

[69]  Yixin Yao,et al.  The PI 3-kinase/Akt signaling pathway is activated due to aberrant Pten expression and targets transcription factors NF-κB and c-Myc in pancreatic cancer cells , 2004, Oncogene.

[70]  A. Baldwin Regulation of cell death and autophagy by IKK and NF‐κB: critical mechanisms in immune function and cancer , 2012, Immunological reviews.

[71]  J. Adams,et al.  Novel IKK inhibitors: beta-carbolines. , 2003, Bioorganic & Medicinal Chemistry Letters.

[72]  D. S. Lind,et al.  Nuclear factor-kappa B is upregulated in colorectal cancer. , 2001, Surgery.

[73]  P. Dent,et al.  Constitutive activation of NF-kappaB in human hepatocellular carcinoma: evidence of a cytoprotective role. , 2006, Human gene therapy.

[74]  G. Dong,et al.  IL (Interleukin)-1α Promotes Nuclear Factor-κB and AP-1-induced IL-8 Expression, Cell Survival, and Proliferation in Head and Neck Squamous Cell Carcinomas , 2001 .

[75]  E. Schmidt,et al.  IKKα Provides an Essential Link between RANK Signaling and Cyclin D1 Expression during Mammary Gland Development , 2001, Cell.

[76]  P. Carmeliet,et al.  Angiogenesis in cancer and other diseases , 2000, Nature.

[77]  C. Turck,et al.  Akt-Dependent Phosphorylation Specifically Regulates Cot Induction of NF-κB-Dependent Transcription , 2002, Molecular and Cellular Biology.

[78]  Alexander Varshavsky,et al.  The ubiquitin system. , 1998, Annual review of biochemistry.

[79]  D. Cortez,et al.  A requirement for NF-κB activation in Bcr–Abl-mediated transformation , 1998 .

[80]  C. Gélinas,et al.  The Rel/NF-κB Family Directly Activates Expression of the Apoptosis Inhibitor Bcl-xL , 2000, Molecular and Cellular Biology.

[81]  D. Carrasco,et al.  The v‐rel oncogene promotes malignant T‐cell leukemia/lymphoma in transgenic mice. , 1996, The EMBO journal.

[82]  Fred Saad,et al.  Nuclear Factor-κB Nuclear Localization Is Predictive of Biochemical Recurrence in Patients with Positive Margin Prostate Cancer , 2004, Clinical Cancer Research.

[83]  M. Karin Nuclear factor-κB in cancer development and progression , 2006, Nature.

[84]  Kuan-Teh Jeang,et al.  Human T-cell leukaemia virus type 1 (HTLV-1) infectivity and cellular transformation , 2007, Nature Reviews Cancer.

[85]  David M. Smith,et al.  Ester Bond-containing Tea Polyphenols Potently Inhibit Proteasome Activity in Vitro and in Vivo * , 2001, The Journal of Biological Chemistry.

[86]  B. Aggarwal,et al.  Nuclear factor-kappaB: a friend or a foe in cancer? , 2004, Biochemical pharmacology.

[87]  J. Romashkova,et al.  NF-κB is a target of AKT in anti-apoptotic PDGF signalling , 1999, Nature.

[88]  G. Chen,et al.  The Nuclear Localization of NFκB and p53 Is Positively Correlated with HPV16 E7 Level in Laryngeal Squamous Cell Carcinoma1 , 2003 .

[89]  N. Perkins Achieving transcriptional specificity with NF-kappa B. , 1997, The international journal of biochemistry & cell biology.

[90]  J. Diao,et al.  X protein of hepatitis B virus modulates cytokine and growth factor related signal transduction pathways during the course of viral infections and hepatocarcinogenesis. , 2001, Cytokine & growth factor reviews.

[91]  S. Manna,et al.  Ectopic Expression of Hepatitis C Virus Core Protein Differentially Regulates Nuclear Transcription Factors , 1998, Journal of Virology.

[92]  C. N. Coleman,et al.  Constitutive activation of IκB kinase α and NF-κB in prostate cancer cells is inhibited by ibuprofen , 1999, Oncogene.

[93]  B. Barlogie,et al.  Antitumor activity of thalidomide in refractory multiple myeloma. , 1999, The New England journal of medicine.

[94]  Masakazu Toi,et al.  Nuclear factor-κB inhibitors as sensitizers to anticancer drugs , 2005, Nature Reviews Cancer.

[95]  J. Adams,et al.  Novel IKK inhibitors: β-carbolines , 2003 .

[96]  W. Zong,et al.  Mechanisms of constitutive NF‐κB activation in human prostate cancer cells , 2002, The Prostate.

[97]  R. Korneluk,et al.  The inhibitors of apoptosis (IAPs) as cancer targets , 2007, Apoptosis.

[98]  A. Baldwin,et al.  Positive and negative regulation of NF-kappaB by COX-2: roles of different prostaglandins. , 2001, The Journal of biological chemistry.

[99]  B. Aggarwal,et al.  Flavopiridol Inhibits NF-κB Activation Induced by Various Carcinogens and Inflammatory Agents through Inhibition of IκBα Kinase and p65 Phosphorylation , 2004, Journal of Biological Chemistry.

[100]  G. Beck,et al.  A Randomized Trial of Aspirin to Prevent Colorectal Adenomas , 2003 .

[101]  D. Altieri,et al.  Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer. , 1998, Cancer research.

[102]  R. Jordan,et al.  Molecular viral oncology of hepatocellular carcinoma , 2003, Oncogene.

[103]  M. Karin,et al.  The two NF-κB activation pathways and their role in innate and adaptive immunity , 2004 .

[104]  Christian Stehlik,et al.  Activation of NF-κB by XIAP, the X Chromosome-linked Inhibitor of Apoptosis, in Endothelial Cells Involves TAK1* , 2000, The Journal of Biological Chemistry.

[105]  G. Sethi,et al.  Potential pharmacological control of the NF-κB pathway. , 2009, Trends in pharmacological sciences.

[106]  Kei Yamamoto,et al.  Transcriptional Roles of Nuclear Factor B and Nuclear Factor-Interleukin-6 in the Tumor Necrosis Factor -Dependent Induction of Cyclooxygenase-2 in MC3T3-E1 Cells (*) , 1995, The Journal of Biological Chemistry.

[107]  Julie S. Jurenka Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research. , 2009, Alternative medicine review : a journal of clinical therapeutic.

[108]  T. McDonnell,et al.  Bcl-2 suppresses apoptosis resulting from disruption of the NF-κB survival pathway , 1997 .

[109]  C. Y. Wang,et al.  Requirement of NF-kappaB activation to suppress p53-independent apoptosis induced by oncogenic Ras. , 1997, Science.

[110]  B. Aggarwal,et al.  Evidence that TNF-TNFR1-TRADD-TRAF2-RIP-TAK1-IKK pathway mediates constitutive NF-κB activation and proliferation in human head and neck squamous cell carcinoma , 2007, Oncogene.

[111]  A. Baldwin,et al.  Role of Transcriptional Activation of IκBα in Mediation of Immunosuppression by Glucocorticoids , 1995, Science.

[112]  M. Karin,et al.  Nuclear cytokine-activated IKKα controls prostate cancer metastasis by repressing Maspin , 2009, Nature.

[113]  D. Schrump,et al.  Inhibition of lung cancer proliferation by antisense cyclin D. , 1996, Cancer gene therapy.

[114]  Debajit K. Biswas,et al.  NF-κB activation in human breast cancer specimens and its role in cell proliferation and apoptosis , 2004 .

[115]  N. Perkins,et al.  NF-κB: tumor promoter or suppressor? , 2004 .

[116]  R. Gaynor,et al.  IKKalpha regulates mitogenic signaling through transcriptional induction of cyclin D1 via Tcf. , 2003, Molecular biology of the cell.

[117]  Y. Ben-Neriah,et al.  NF-κB functions as a tumour promoter in inflammation-associated cancer , 2004, Nature.

[118]  C. Van Waes,et al.  Expression of a dominant-negative mutant inhibitor-kappaBalpha of nuclear factor-kappaB in human head and neck squamous cell carcinoma inhibits survival, proinflammatory cytokine expression, and tumor growth in vivo. , 1999, Cancer research.

[119]  F. Greten,et al.  IKK/NF‐κB and STAT3 pathways: central signalling hubs in inflammation‐mediated tumour promotion and metastasis , 2009, EMBO reports.

[120]  Barbara A. Murphy,et al.  Gene Expression Profiles Identify Epithelial-to-Mesenchymal Transition and Activation of Nuclear Factor-κB Signaling as Characteristics of a High-risk Head and Neck Squamous Cell Carcinoma , 2006 .

[121]  R. Kyle,et al.  Multiple myeloma. , 2008, Blood.

[122]  F. Schmitz,et al.  Increased Expression of RelA/Nuclear Factor-κB Protein Correlates with Colorectal Tumorigenesis , 2003, Oncology.

[123]  A. Baldwin,et al.  Inhibition of NF-kappa B activity by thalidomide through suppression of IkappaB kinase activity. , 2001, The Journal of biological chemistry.

[124]  B. Aggarwal,et al.  Epidermal growth factor (EGF) activates nuclear factor-κB through IκBα kinase-independent but EGF receptor-kinase dependent tyrosine 42 phosphorylation of IκBα , 2007, Oncogene.

[125]  C. Van Waes,et al.  IL (interleukin)-1alpha promotes nuclear factor-kappaB and AP-1-induced IL-8 expression, cell survival, and proliferation in head and neck squamous cell carcinomas. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[126]  S. Ghosh,et al.  Shared Principles in NF-κB Signaling , 2008, Cell.

[127]  L. Norton,et al.  Microtubule-interfering Agents Stimulate the Transcription of Cyclooxygenase-2 , 2000, The Journal of Biological Chemistry.

[128]  V. Tergaonkar NFkappaB pathway: a good signaling paradigm and therapeutic target. , 2006, The international journal of biochemistry & cell biology.

[129]  Joseph A. DiDonato,et al.  Immunosuppression by Glucocorticoids: Inhibition of NF-κB Activity Through Induction of IκB Synthesis , 1995, Science.

[130]  Robert E. Brown,et al.  Overexpression of phosphorylated nuclear factor-kappa B in tonsillar squamous cell carcinoma and high-grade dysplasia is associated with poor prognosis , 2005, Modern Pathology.

[131]  R. Carrasco,et al.  Pathogenesis of myeloma. , 2011, Annual review of pathology.

[132]  J. Keats,et al.  Classical and/or alternative NF-kappaB pathway activation in multiple myeloma. , 2010, Blood.

[133]  R. Gaynor,et al.  The anti-inflammatory agents aspirin and salicylate inhibit the activity of I(kappa)B kinase-beta. , 1998, Nature.

[134]  R. Kyle,et al.  Drug therapy: Multiple myeloma , 2004 .

[135]  L. Pfeffer,et al.  NF-κB activation by tumour necrosis factor requires the Akt serine–threonine kinase , 1999, Nature.

[136]  Marty W. Mayo,et al.  NF-k B Antiapoptosis : Induction of TRAF 1 and TRAF 2 and c-IAP 1 and c-IAP 2 to Suppress Caspase-8 Activation , 1998 .

[137]  Y. Surh,et al.  Cancer chemoprevention with dietary phytochemicals , 2003, Nature Reviews Cancer.

[138]  R. Coffey,et al.  Her-2/neu overexpression induces NF-κB via a PI3-kinase/Akt pathway involving calpain-mediated degradation of IκB-α that can be inhibited by the tumor suppressor PTEN , 2001, Oncogene.

[139]  G. Sethi,et al.  Targeting transcription factor NF-kappaB to overcome chemoresistance and radioresistance in cancer therapy. , 2010, Biochimica et biophysica acta.

[140]  James R. Burke,et al.  BMS-345541 Is a Highly Selective Inhibitor of IκB Kinase That Binds at an Allosteric Site of the Enzyme and Blocks NF-κB-dependent Transcription in Mice* , 2003, The Journal of Biological Chemistry.

[141]  B. Salh,et al.  5,6-Dichloro-ribifuranosylbenzimidazole- and apigenin-induced sensitization of colon cancer cells to TNF-alpha-mediated apoptosis. , 2003, American journal of physiology. Gastrointestinal and liver physiology.

[142]  N. Normanno,et al.  Epidermal growth factor receptor (EGFR) signaling in cancer. , 2006, Gene.

[143]  M. Resnick,et al.  Constitutive activation of P I3 K-Akt and NF-kappaB during prostate cancer progression in autochthonous transgenic mouse model. , 2005, The Prostate.

[144]  James B. Mitchell,et al.  Nuclear Factor-κB is an Important Modulator of the Altered Gene Expression Profile and Malignant Phenotype in Squamous Cell Carcinoma , 2004, Cancer Research.

[145]  M. Malim,et al.  Suppression of tumor necrosis factor-induced cell death by inhibitor of apoptosis c-IAP2 is under NF-kappaB control. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[146]  Hua Yu,et al.  STATs in cancer inflammation and immunity: a leading role for STAT3 , 2009, Nature Reviews Cancer.

[147]  Francesca Zazzeroni,et al.  Linking JNK signaling to NF-κB: a key to survival , 2004, Journal of Cell Science.

[148]  Francesca Zazzeroni,et al.  Linking JNK signaling to NF-kappaB: a key to survival. , 2004, Journal of cell science.

[149]  D. Cortez,et al.  A requirement for NF-kappaB activation in Bcr-Abl-mediated transformation. , 1998, Genes & development.

[150]  M. Karin,et al.  Dangerous liaisons: STAT3 and NF-kappaB collaboration and crosstalk in cancer. , 2010, Cytokine & growth factor reviews.

[151]  Junji Kato,et al.  Hepatitis C virus core protein promotes proliferation of human hepatoma cells through enhancement of transforming growth factor α expression via activation of nuclear factor-κB , 2006, Gut.

[152]  M. Mayo,et al.  Akt Suppresses Apoptosis by Stimulating the Transactivation Potential of the RelA/p65 Subunit of NF-κB , 2000, Molecular and Cellular Biology.

[153]  J. Schmid,et al.  BMS-345541 targets inhibitor of kappaB kinase and induces apoptosis in melanoma: involvement of nuclear factor kappaB and mitochondria pathways. , 2006, Clinical cancer research : an official journal of the American Association for Cancer Research.

[154]  M. Karin,et al.  Regulation and function of NF-kappaB transcription factors in the immune system. , 2009, Annual review of immunology.

[155]  G. Dong,et al.  Expression of a Dominant-Negative Mutant Inhibitor-κBα of Nuclear Factor-κB in Human Head and Neck Squamous Cell Carcinoma Inhibits Survival, Proinflammatory Cytokine Expression, and Tumor Growth in Vivo , 1999 .

[156]  N. Perkins NF-kappaB: tumor promoter or suppressor? , 2004, Trends in cell biology.

[157]  M J May,et al.  NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. , 1998, Annual review of immunology.

[158]  R. Orlowski,et al.  The proteasome and proteasome inhibitors in cancer therapy. , 2006, Annual review of pharmacology and toxicology.

[159]  Bart Barlogie,et al.  A phase 2 study of bortezomib in relapsed, refractory myeloma. , 2003, The New England journal of medicine.

[160]  K. Anderson,et al.  Molecular mechanisms mediating antimyeloma activity of proteasome inhibitor PS-341. , 2003, Blood.

[161]  Han-Ming Shen,et al.  NFκB signaling in carcinogenesis and as a potential molecular target for cancer therapy , 2009, Apoptosis.

[162]  Douglas B. Evans,et al.  NF-kappaB and AP-1 connection: mechanism of NF-kappaB-dependent regulation of AP-1 activity. , 2004, Molecular and cellular biology.

[163]  Sankar Ghosh,et al.  Signaling to NF-kappaB. , 2004, Genes & development.

[164]  A. Baldwin,et al.  Role of transcriptional activation of I kappa B alpha in mediation of immunosuppression by glucocorticoids. , 1995, Science.

[165]  C. Bucana,et al.  Nuclear Factor-κB Activity Correlates with Growth, Angiogenesis, and Metastasis of Human Melanoma Cells in Nude Mice , 2000 .

[166]  N. Ueda,et al.  Transcriptional roles of nuclear factor kappa B and nuclear factor-interleukin-6 in the tumor necrosis factor alpha-dependent induction of cyclooxygenase-2 in MC3T3-E1 cells. , 1995, The Journal of biological chemistry.

[167]  A. Markham,et al.  Expression of the antiapoptosis gene,Survivin, predicts death from recurrent colorectal carcinoma , 2000, Gut.

[168]  H. Patel,et al.  Cross-talk between transcription factors NF-kappa B and C/EBP in the transcriptional regulation of genes. , 1997, The international journal of biochemistry & cell biology.

[169]  Michael Karin,et al.  NF-κB at the crossroads of life and death , 2002, Nature Immunology.

[170]  H. Nakshatri,et al.  NF-κ B Promotes Breast Cancer Cell Migration and Metastasis by Inducing the Expression of the Chemokine Receptor CXCR4* , 2003, Journal of Biological Chemistry.

[171]  J. McCubrey,et al.  Signal transduction mediated by the Ras/Raf/MEK/ERK pathway from cytokine receptors to transcription factors: potential targeting for therapeutic intervention , 2003, Leukemia.

[172]  J. Geng,et al.  Andrographolide Attenuates Inflammation by Inhibition of NF-κB Activation through Covalent Modification of Reduced Cysteine 62 of p501 , 2004, The Journal of Immunology.

[173]  L. Young,et al.  Epstein–Barr virus: 40 years on , 2004, Nature Reviews Cancer.

[174]  Francesca Zazzeroni,et al.  Induction of gadd45β by NF-κB downregulates pro-apoptotic JNK signalling , 2001, Nature.

[175]  A. Siddiqui,et al.  Hepatitis C Virus NS5A and Subgenomic Replicon Activate NF-κB via Tyrosine Phosphorylation of IκBα and Its Degradation by Calpain Protease* , 2003, Journal of Biological Chemistry.

[176]  Hua Yu,et al.  Persistently activated Stat3 maintains constitutive NF-kappaB activity in tumors. , 2009, Cancer cell.

[177]  P. Elliott,et al.  Enhanced chemosensitivity to CPT-11 with proteasome inhibitor PS-341: implications for systemic nuclear factor-kappaB inhibition. , 2001, Cancer research.

[178]  P. L. Bergsagel,et al.  Advances in biology of multiple myeloma: clinical applications. , 2004, Blood.

[179]  K. Ang,et al.  Potentiation of tumor response to radiation or chemoradiation by selective cyclooxygenase-2 enzyme inhibitors. , 2004, International journal of radiation oncology, biology, physics.

[180]  Michael Karin,et al.  The IKK NF-κB system: a treasure trove for drug development , 2004, Nature Reviews Drug Discovery.

[181]  A. Baldwin,et al.  THE NF-κB AND IκB PROTEINS: New Discoveries and Insights , 1996 .

[182]  B. Aggarwal,et al.  Thalidomide Suppresses NF-κB Activation Induced by TNF and H2O2, But Not That Activated by Ceramide, Lipopolysaccharides, or Phorbol Ester1 , 2002, The Journal of Immunology.

[183]  M. Karin,et al.  IκB kinase α kinase activity is required for self-renewal of ErbB2/Her2-transformed mammary tumor-initiating cells , 2007, Proceedings of the National Academy of Sciences.

[184]  R. Cardiff,et al.  Protein kinase CK2 in mammary gland tumorigenesis , 2001, Oncogene.

[185]  C. N. Coleman,et al.  Constitutive activation of IkappaB kinase alpha and NF-kappaB in prostate cancer cells is inhibited by ibuprofen. , 1999, Oncogene.

[186]  R. Gaynor,et al.  Sulindac Inhibits Activation of the NF-κB Pathway* , 1999, The Journal of Biological Chemistry.

[187]  Harikrishna Nakshatri,et al.  Antitumor agent parthenolide reverses resistance of breast cancer cells to tumor necrosis factor-related apoptosis-inducing ligand through sustained activation of c-Jun N-terminal kinase , 2004, Oncogene.

[188]  Pascal Meier,et al.  IAPs: from caspase inhibitors to modulators of NF-κB, inflammation and cancer , 2010, Nature Reviews Cancer.

[189]  Sankar Ghosh,et al.  NF-kappa B activation in human breast cancer specimens and its role in cell proliferation and apoptosis. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[190]  Michael Karin,et al.  NF-kappaB at the crossroads of life and death. , 2002, Nature immunology.

[191]  Rolf Larsson,et al.  A Phase I study of CHS 828 in patients with solid tumor malignancy. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[192]  W. Funkhouser,et al.  Selective activation of NF-kappa B subunits in human breast cancer: potential roles for NF-kappa B2/p52 and for Bcl-3. , 2000, Oncogene.

[193]  K. Okumura,et al.  Reactive oxygen species mediate crosstalk between NF-κB and JNK , 2006, Cell Death and Differentiation.

[194]  G. Courtois,et al.  Mutations in the NF-kappaB signaling pathway: implications for human disease. , 2006, Oncogene.

[195]  A. Ray,et al.  Physical association and functional antagonism between the p65 subunit of transcription factor NF-kappa B and the glucocorticoid receptor. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[196]  L. Staudt,et al.  Small molecule inhibitors of IκB kinase are selectively toxic for subgroups of diffuse large B-cell lymphoma defined by gene expression profiling , 2005 .

[197]  C. Van Waes,et al.  Constitutive activation of transcription factors NF‐κB, AP‐1, and NF‐IL6 in human head and neck squamous cell carcinoma cell lines that express pro‐inflammatory and pro‐angiogenic cytokines , 1999, Molecular carcinogenesis.

[198]  J. Adams The proteasome: a suitable antineoplastic target , 2004, Nature Reviews Cancer.

[199]  T. Hunter,et al.  Cyclins and cancer II: Cyclin D and CDK inhibitors come of age , 1994, Cell.

[200]  B. Levine,et al.  Cyclooxygenase-2 inhibition with celecoxib enhances antitumor efficacy and reduces diarrhea side effect of CPT-11. , 2002, Cancer research.

[201]  T. Libermann,et al.  Molecular sequelae of proteasome inhibition in human multiple myeloma cells , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[202]  Y. Liaw,et al.  Constitutive activation of nuclear factor κB in hepatocellular carcinoma , 2000 .

[203]  R. Schmid,et al.  Mechanisms of Bcr-Abl-mediated NF-kappaB/Rel activation. , 2003, Experimental hematology.

[204]  Claus Scheidereit,et al.  NF-κB Function in Growth Control: Regulation of Cyclin D1 Expression and G0/G1-to-S-Phase Transition , 1999, Molecular and Cellular Biology.

[205]  C. Waes,et al.  Factor ( s ) in Head and Neck Squamous Carcinoma Cells B Activation by Serum κ Kinase and Aberrant Nuclear Factor-B κ Protein Kinase Casein Kinase 2 Mediates Inhibitor-Updated , 2006 .

[206]  Hyung Jin Kim,et al.  Vascular Endothelial Growth Factor Expression of Intercellular Adhesion Molecule 1 (ICAM-1), Vascular Cell Adhesion Molecule 1 (VCAM-1), and E-selectin through Nuclear Factor-κB Activation in Endothelial Cells* , 2001, The Journal of Biological Chemistry.

[207]  B. Aggarwal,et al.  Epidermal growth factor (EGF) activates nuclear factor-kappaB through IkappaBalpha kinase-independent but EGF receptor-kinase dependent tyrosine 42 phosphorylation of IkappaBalpha. , 2007, Oncogene.

[208]  I. Herr,et al.  Cellular stress response and apoptosis in cancer therapy. , 2001, Blood.

[209]  M. Mayo,et al.  Modulation of NF‐κB‐dependent transcription and cell survival by the SIRT1 deacetylase , 2004, The EMBO journal.

[210]  R. I. Carey,et al.  Cyclooxygenase‐2 inhibitor celecoxib augments chemotherapeutic drug‐induced apoptosis by enhancing activation of caspase‐3 and ‐9 in prostate cancer cells , 2005, International journal of cancer.

[211]  C. Van Waes,et al.  Coexpression of proangiogenic factors IL-8 and VEGF by human head and neck squamous cell carcinoma involves coactivation by MEK-MAPK and IKK-NF-kappaB signal pathways. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[212]  M. Arsura,et al.  Nuclear factor-κB and liver carcinogenesis , 2005 .

[213]  Andrew J. Dannenberg,et al.  Regulation of Cyclooxgenase-2 mRNA Stability by Taxanes , 2003, Journal of Biological Chemistry.

[214]  W. Greene,et al.  Cross‐coupling of the NF‐kappa B p65 and Fos/Jun transcription factors produces potentiated biological function. , 1993, The EMBO journal.

[215]  A. MacKenzie,et al.  The inhibitors of apoptosis (IAPs) and their emerging role in cancer , 1998, Oncogene.

[216]  Christian Stehlik,et al.  Nuclear Factor (NF)-κB–regulated X-chromosome–linked iap Gene Expression Protects Endothelial Cells from Tumor Necrosis Factor α–induced Apoptosis , 1998, The Journal of experimental medicine.

[217]  Bharat B. Aggarwal,et al.  Nuclear factor-κB: its role in health and disease , 2004, Journal of Molecular Medicine.

[218]  F. Schmitz,et al.  Increased expression of RelA/nuclear factor-kappa B protein correlates with colorectal tumorigenesis. , 2003, Oncology.

[219]  F. Rapp,et al.  Thymidine Kinase Activity in Burkitt Lymphoblastoid Somatic Cell Hybrids After Induction of the EB Virus 1 , 1973, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[220]  S. Deventer,et al.  NF-kappaB, p38 MAPK and JNK are highly expressed and active in the stroma of human colonic adenomatous polyps , 2001, Oncogene.

[221]  A. Baldwin,et al.  The NF-kappa B and I kappa B proteins: new discoveries and insights. , 1996, Annual review of immunology.

[222]  R. DuBois,et al.  PROSTAGLANDINS AND CANCER , 2005, Gut.

[223]  S. Lemon,et al.  Virus-specific mechanisms of carcinogenesis in hepatitis C virus associated liver cancer , 2011, Oncogene.

[224]  B. Rayet,et al.  Aberrant rel/nfkb genes and activity in human cancer , 1999, Oncogene.

[225]  C. Pham,et al.  The NF-κB-mediated control of the JNK cascade in the antagonism of programmed cell death in health and disease , 2006, Cell Death and Differentiation.

[226]  C. Bucana,et al.  Blockade of nuclear factor-kappaB signaling inhibits angiogenesis and tumorigenicity of human ovarian cancer cells by suppressing expression of vascular endothelial growth factor and interleukin 8. , 2000, Cancer research.

[227]  S. Bailey,et al.  Nuclear factor-kappaB activation: a molecular therapeutic target for estrogen receptor-negative and epidermal growth factor receptor family receptor-positive human breast cancer. , 2007, Molecular cancer therapeutics.

[228]  L. Staudt,et al.  Differential efficacy of bortezomib plus chemotherapy within molecular subtypes of diffuse large B-cell lymphoma. , 2009, Blood.

[229]  C. Le Page,et al.  EGFR and Her‐2 regulate the constitutive activation of NF‐kappaB in PC‐3 prostate cancer cells , 2005, The Prostate.

[230]  B. Aggarwal,et al.  Nonsteroidal anti-inflammatory agents differ in their ability to suppress NF-kappaB activation, inhibition of expression of cyclooxygenase-2 and cyclin D1, and abrogation of tumor cell proliferation. , 2004, Oncogene.

[231]  M. C. Hu,et al.  HER-2/neu blocks tumor necrosis factor-induced apoptosis via the Akt/NF-kappaB pathway. , 2000, The Journal of biological chemistry.

[232]  W. Greene,et al.  Shaping the nuclear action of NF-κB , 2004, Nature Reviews Molecular Cell Biology.

[233]  R. Gaynor,et al.  Constitutive activation of NF-κB in Ki-ras-transformed prostate epithelial cells , 2002, Oncogene.

[234]  Marty W. Mayo,et al.  NF-κB Induces Expression of the Bcl-2 Homologue A1/Bfl-1 To Preferentially Suppress Chemotherapy-Induced Apoptosis , 1999, Molecular and Cellular Biology.

[235]  D. Saluja,et al.  Differential expression and activation of NF‐κB family proteins during oral carcinogenesis: Role of high risk human papillomavirus infection , 2006 .

[236]  S. Thorgeirsson,et al.  Transforming Growth Factor-α Inhibits the Intrinsic Pathway of c-Myc-Induced Apoptosis through Activation of Nuclear Factor-κB in Murine Hepatocellular Carcinomas , 2005, Molecular Cancer Research.

[237]  Michael Karin,et al.  IKKβ Couples Hepatocyte Death to Cytokine-Driven Compensatory Proliferation that Promotes Chemical Hepatocarcinogenesis , 2005, Cell.

[238]  R. Gaynor,et al.  Formation of an IKKalpha-dependent transcription complex is required for estrogen receptor-mediated gene activation. , 2005, Molecular cell.

[239]  A. Baldwin,et al.  Nuclear factor-kappaB and inhibitor of kappaB kinase pathways in oncogenic initiation and progression. , 2006, Oncogene.

[240]  P. Kloetzel,et al.  Green Tea Epigallocatechin-3-Gallate Mediates T Cellular NF-κB Inhibition and Exerts Neuroprotection in Autoimmune Encephalomyelitis1 , 2004, The Journal of Immunology.

[241]  T. Gilmore Multiple mutations contribute to the oncogenicity of the retroviral oncoprotein v-Rel , 1999, Oncogene.

[242]  S. Yamaoka,et al.  Constitutive activation of NF‐kappa B is essential for transformation of rat fibroblasts by the human T‐cell leukemia virus type I Tax protein. , 1996, The EMBO journal.

[243]  J. Cheng,et al.  Tumour-infiltrating regulatory T cells stimulate mammary cancer metastasis through RANKL–RANK signalling , 2011, Nature.

[244]  H. Nakayama,et al.  High expression levels of nuclear factor κB, IκB kinase α and Akt kinase in squamous cell carcinoma of the oral cavity , 2001 .

[245]  D. Altieri,et al.  Expression of a novel antiapoptosis gene, survivin, correlated with tumor cell apoptosis and p53 accumulation in gastric carcinomas. , 1998, Cancer research.

[246]  R. Weindruch,et al.  Effect of antioxidants on androgen-induced AP-1 and NF-kappaB DNA-binding activity in prostate carcinoma cells. , 1999, Journal of the National Cancer Institute.

[247]  D. S. Lind,et al.  Nuclear factor-κB is upregulated in colorectal cancer , 2001 .

[248]  Andreas Sommer,et al.  NF-κB is essential for epithelial-mesenchymal transition and metastasis in a model of breast cancer progression , 2004 .

[249]  M. Merville,et al.  Phosphorylation of NF-κB and IκB proteins: implications in cancer and inflammation , 2005 .

[250]  D. W. Kim,et al.  Mouse Mammary Tumor Virus c-rel Transgenic Mice Develop Mammary Tumors , 2003, Molecular and Cellular Biology.

[251]  M. Hatano,et al.  Transcriptional activation of survivin through the NF‐κB pathway by human T‐cell leukemia virus type I tax , 2005, International journal of cancer.

[252]  A. Thiel,et al.  The IκB Kinase Complex and NF-κB Actas Master Regulators of Lipopolysaccharide-Induced Gene Expressionand Control Subordinate Activation ofAP-1 , 2004, Molecular and Cellular Biology.

[253]  T. Hunter,et al.  Cyclins and cancer , 1991, Cell.

[254]  B. Dörken,et al.  Constitutive nuclear factor-kappaB-RelA activation is required for proliferation and survival of Hodgkin's disease tumor cells. , 1997, The Journal of clinical investigation.

[255]  C Gélinas,et al.  The Rel/NF-kappaB family directly activates expression of the apoptosis inhibitor Bcl-x(L). , 2000, Molecular and cellular biology.

[256]  Vinay Tergaonkar,et al.  NFκB pathway: A good signaling paradigm and therapeutic target , 2006 .

[257]  W. Zong,et al.  The prosurvival Bcl-2 homolog Bfl-1/A1 is a direct transcriptional target of NF-κB that blocks TNFα-induced apoptosis , 1999 .

[258]  R. Gaynor,et al.  Sulindac inhibits activation of the NF-kappaB pathway. , 1999, The Journal of biological chemistry.

[259]  A. Siddiqui,et al.  Hepatitis C virus NS5A and subgenomic replicon activate NF-kappaB via tyrosine phosphorylation of IkappaBalpha and its degradation by calpain protease. , 2003, The Journal of biological chemistry.

[260]  M. Karin,et al.  Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway. , 2001, Science.

[261]  T. Slaga,et al.  The role of IKK in constitutive activation of NF-kappaB transcription factor in prostate carcinoma cells. , 2002, Journal of cell science.

[262]  Francesca Zazzeroni,et al.  Ferritin Heavy Chain Upregulation by NF-κB Inhibits TNFα-Induced Apoptosis by Suppressing Reactive Oxygen Species , 2004, Cell.

[263]  Ulrich Siebenlist,et al.  Constitutive Nuclear Factor κB Activity Is Required for Survival of Activated B Cell–like Diffuse Large B Cell Lymphoma Cells , 2001, The Journal of experimental medicine.

[264]  M. Madsen,et al.  Anticancer agent CHS 828 suppresses nuclear factor‐κB activity in cancer cells through downregulation of IKK activity , 2004, International Journal of Cancer.

[265]  M. R. Hellmich,et al.  Bombesin stimulates nuclear factor kappa B activation and expression of proangiogenic factors in prostate cancer cells. , 2003, Cancer research.

[266]  S. Baird,et al.  IAP-targeted therapies for cancer , 2008, Oncogene.

[267]  Inder M Verma,et al.  NF-kappaB regulation in the immune system. , 2002, Nature reviews. Immunology.

[268]  L. Bruhn,et al.  Promiscuous mutations activate the noncanonical NF-kappaB pathway in multiple myeloma. , 2007, Cancer cell.

[269]  Shishir Shishodia,et al.  Molecular targets of dietary agents for prevention and therapy of cancer. , 2006, Biochemical pharmacology.

[270]  D. Baltimore,et al.  Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell 1986. 46: 705-716. , 2006, Journal of immunology.

[271]  Markus Müller,et al.  Activation of NF-κB Is Essential for Hepatocyte Growth Factor-Mediated Proliferation and Tubulogenesis , 2002, Molecular and Cellular Biology.

[272]  M. Bouchard,et al.  The Enigmatic X Gene of Hepatitis B Virus , 2004, Journal of Virology.

[273]  N. Munshi,et al.  Apoptotic signaling induced by immunomodulatory thalidomide analogs in human multiple myeloma cells: therapeutic implications. , 2002, Blood.

[274]  T. Skov,et al.  CHS 828, a novel pyridyl cyanoguanidine with potent antitumor activity in vitro and in vivo. , 1999, Cancer research.

[275]  M. Karin,et al.  Inhibition of NF-κB in cancer cells converts inflammation- induced tumor growth mediated by TNFα to TRAIL-mediated tumor regression , 2004 .

[276]  Y. Surh,et al.  Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-kappa B activation. , 2001, Mutation research.

[277]  M. Roizen,et al.  Hallmarks of Cancer: The Next Generation , 2012 .

[278]  M. Karin,et al.  Immunosuppression by glucocorticoids: inhibition of NF-kappa B activity through induction of I kappa B synthesis. , 1995, Science.

[279]  R. Schmid,et al.  Mechanisms of Bcr-Abl-mediated NF-κB/Rel activation , 2003 .

[280]  Razelle Kurzrock,et al.  Phase II Trial of Curcumin in Patients with Advanced Pancreatic Cancer , 2008, Clinical Cancer Research.

[281]  R. Coffey,et al.  Her-2/neu overexpression induces NF-kappaB via a PI3-kinase/Akt pathway involving calpain-mediated degradation of IkappaB-alpha that can be inhibited by the tumor suppressor PTEN. , 2001, Oncogene.

[282]  Chris Twelves,et al.  Phase I study and pharmacokinetic of CHS-828, a guanidino-containing compound, administered orally as a single dose every 3 weeks in solid tumours: an ECSG/EORTC study. , 2005, European journal of cancer.

[283]  C. Van Waes,et al.  Effects of pharmacologic antagonists of epidermal growth factor receptor, PI3K and MEK signal kinases on NF‐κB and AP‐1 activation and IL‐8 and VEGF expression in human head and neck squamous cell carcinoma lines , 2002, International journal of cancer.

[284]  D. Saluja,et al.  Differential expression and activation of NF-kappaB family proteins during oral carcinogenesis: Role of high risk human papillomavirus infection. , 2006, International journal of cancer.

[285]  L. Staudt,et al.  Frequent engagement of the classical and alternative NF-kappaB pathways by diverse genetic abnormalities in multiple myeloma. , 2007, Cancer cell.

[286]  R. Chetty,et al.  Cyclin D1 and human neoplasia. , 1998, Molecular pathology : MP.

[287]  David A. Cheresh,et al.  Nuclear cytokine-activated IKKα controls prostate cancer metastasis by repressing Maspin , 2007, Nature.

[288]  T. Shono,et al.  Involvement of interleukin-8, vascular endothelial growth factor, and basic fibroblast growth factor in tumor necrosis factor alpha-dependent angiogenesis , 1997, Molecular and cellular biology.

[289]  D. Seldin,et al.  Roles of IKK kinases and protein kinase CK2 in activation of nuclear factor-kappaB in breast cancer. , 2001, Cancer research.

[290]  H. Pahl,et al.  The Anti-inflammatory Sesquiterpene Lactone Helenalin Inhibits the Transcription Factor NF-κB by Directly Targeting p65* , 1998, The Journal of Biological Chemistry.

[291]  Alain C. Mita,et al.  Survivin: Key Regulator of Mitosis and Apoptosis and Novel Target for Cancer Therapeutics , 2008, Clinical Cancer Research.

[292]  M. Nieto,et al.  Inflammation and EMT: an alliance towards organ fibrosis and cancer progression , 2009, EMBO molecular medicine.

[293]  M. Korc,et al.  Inhibition of basal and mitogen-stimulated pancreatic cancer cell growth by cyclin D1 antisense is associated with loss of tumorigenicity and potentiation of cytotoxicity to cisplatinum. , 1998, The Journal of clinical investigation.

[294]  B. Aggarwal,et al.  Cigarette smoke condensate activates nuclear transcription factor-κB through phosphorylation and degradation of IκBα: correlation with induction of cyclooxygenase-2 , 2002 .

[295]  Michael Karin,et al.  NF-κB in cancer: from innocent bystander to major culprit , 2002, Nature Reviews Cancer.

[296]  R. Everson,et al.  Aspirin Use and Lung, Colon, and Breast Cancer Incidence in a Prospective Study , 1994, Epidemiology.

[297]  Zhiwei Wang,et al.  Retracted: Notch‐1 down‐regulation by curcumin is associated with the inhibition of cell growth and the induction of apoptosis in pancreatic cancer cells , 2006, Cancer.

[298]  D. Kalaitzidis,et al.  The c-Rel transcription factor and B-cell proliferation: a deal with the devil , 2004, Oncogene.

[299]  W. Gerald,et al.  NF-kappaB regulates androgen receptor expression and prostate cancer growth. , 2009, The American journal of pathology.

[300]  M. Karin Nuclear factor-kappaB in cancer development and progression. , 2006, Nature.

[301]  S. Catz,et al.  Transcriptional regulation of bcl-2 by nuclear factor κB and its significance in prostate cancer , 2001, Oncogene.

[302]  Chris Albanese,et al.  NF-κB Controls Cell Growth and Differentiation through Transcriptional Regulation of Cyclin D1 , 1999, Molecular and Cellular Biology.

[303]  W. Greene,et al.  Shaping the nuclear action of NF-kappaB. , 2004, Nature reviews. Molecular cell biology.

[304]  N. Munshi,et al.  NF-κB as a Therapeutic Target in Multiple Myeloma* , 2002, The Journal of Biological Chemistry.

[305]  A. Baldwin,et al.  Inhibition of NF-κB Activity by Thalidomide through Suppression of IκB Kinase Activity* , 2001, The Journal of Biological Chemistry.

[306]  Michael Karin,et al.  Activation by IKKα of a Second, Evolutionary Conserved, NF-κB Signaling Pathway , 2001, Science.

[307]  Yixin Yao,et al.  The PI 3-kinase/Akt signaling pathway is activated due to aberrant Pten expression and targets transcription factors NF-κB and c-Myc in pancreatic cancer cells , 2005, Oncogene.

[308]  Michael Karin,et al.  NF-kappaB in cancer: from innocent bystander to major culprit. , 2002, Nature reviews. Cancer.

[309]  K Takada,et al.  Hepatitis C virus core protein promotes proliferation of human hepatoma cells through enhancement of transforming growth factor alpha expression via activation of nuclear factor-kappaB. , 2006, Gut.

[310]  C. Van Waes,et al.  Role of activated nuclear factor‐κB in the pathogenesis and therapy of squamous cell carcinoma of the head and neck , 2007, Head & neck.

[311]  S. Westerheide,et al.  The Putative Oncoprotein Bcl-3 Induces Cyclin D1 To Stimulate G1 Transition , 2001, Molecular and Cellular Biology.

[312]  P. Lin,et al.  Endothelial cell adhesion molecules and cancer progression. , 2007, Current medicinal chemistry.

[313]  Y. Yarden The EGFR family and its ligands in human cancer. signalling mechanisms and therapeutic opportunities. , 2001, European journal of cancer.

[314]  David Baltimore,et al.  Multiple nuclear factors interact with the immunoglobulin enhancer sequences , 1986, Cell.

[315]  J C Reed,et al.  IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs. , 1998, Cancer research.

[316]  Michael Karin,et al.  IKKβ Links Inflammation and Tumorigenesis in a Mouse Model of Colitis-Associated Cancer , 2004, Cell.

[317]  I. Schieren,et al.  Antisense to cyclin D1 inhibits growth and reverses the transformed phenotype of human esophageal cancer cells. , 1995, Oncogene.

[318]  C. Der,et al.  Oncogenic Ha-Ras-induced Signaling Activates NF-κB Transcriptional Activity, Which Is Required for Cellular Transformation* , 1997, The Journal of Biological Chemistry.