Potential role of Anxa1 in cancer.

The annexins are a well-known, closely related, multigene superfamily of Ca(2+)-regulated, phospholipid-dependent, membrane-binding proteins. As a member of the annexins, Anxa1 participates in a variety of important biological processes, such as cellular transduction, membrane aggregation, inflammation, phagocytosis, proliferation, differentiation and apoptosis. Accumulated evidence has indicated that Anxa1 deregulations are associated with the development, invasion, metastasis, occurrence and drug resistance of cancers. The research evidence in recent years indicates that Anxa1 might specifically function either as a tumor suppressor or a tumor promoter candidate for certain cancers depending on the particular type of tumor cells/tissues. This article summarizes the associations between Anxa1 and malignant tumors, as well as potential action mechanisms. Anxa1 has the potential to be used in the future as a biomarker for the diagnosis, treatment and prognosis of certain tumors.

[1]  M. Festa,et al.  The Involvement of Xanthohumol in the Expression of Annexin in Human Malignant Glioblastoma Cells , 2013, The open biochemistry journal.

[2]  Y. Jeng,et al.  Nuclear localization of annexin A1 is a prognostic factor in oral squamous cell carcinoma , 2008, Journal of surgical oncology.

[3]  M. Hickey,et al.  Deficiency of Annexin A1 in CD4+ T Cells Exacerbates T Cell–Dependent Inflammation , 2013, The Journal of Immunology.

[4]  N. Hu,et al.  Tissue microarray analysis reveals a tight correlation between protein expression pattern and progression of esophageal squamous cell carcinoma , 2006, BMC Cancer.

[5]  S. Nelson,et al.  Loss of annexin A1 expression in human breast cancer detected by multiple high-throughput analyses. , 2004, Biochemical and biophysical research communications.

[6]  Yanqing Ding,et al.  Protein and mRNA Characterization in Human Colorectal Carcinoma Cell Lines with Different Metastatic Potentials , 2007, Cancer investigation.

[7]  M. Schuliga,et al.  Annexin‐1 signals mitogen‐stimulated breast tumor cell proliferation by activation of the formyl peptide receptors (FPRs) 1 and 2 , 2011, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[8]  M Dietel,et al.  Increased expression of annexin I and thioredoxin detected by two-dimensional gel electrophoresis of drug resistant human stomach cancer cells. , 1998, Journal of biochemical and biophysical methods.

[9]  Sindeval José da Silva,et al.  Expression of annexin A1 mRNA in peripheral blood from oral squamous cell carcinoma patients. , 2010, Oral oncology.

[10]  A. Rosengarth,et al.  X-ray structure of full-length annexin 1 and implications for membrane aggregation. , 2001, Journal of molecular biology.

[11]  S. Moss,et al.  Annexins: from structure to function. , 2002, Physiological reviews.

[12]  Nan Hu,et al.  2D Differential In-gel Electrophoresis for the Identification of Esophageal Scans Cell Cancer-specific Protein Markers* , 2002, Molecular & Cellular Proteomics.

[13]  Ming-Tsan Lin,et al.  Annexin A1 is associated with gastric cancer survival and promotes gastric cancer cell invasiveness through the formyl peptide receptor/extracellular signal‐regulated kinase/integrin beta‐1‐binding protein 1 pathway , 2012, Cancer.

[14]  S. Oliani,et al.  Expression of Annexin-A1 and Galectin-1 Anti-Inflammatory Proteins and mRNA in Chronic Gastritis and Gastric Cancer , 2013, Mediators of inflammation.

[15]  S. Hanash,et al.  Occurrence of autoantibodies to annexin I, 14-3-3 theta and LAMR1 in prediagnostic lung cancer sera. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  M. Sun,et al.  The association of annexin A2 and cancers , 2012, Clinical and Translational Oncology.

[17]  R. Gillet,et al.  Annexin 1 expression and phosphorylation are upregulated during liver regeneration and transformation in antithrombin iii sv40 t large antigen transgenic mice , 2000, Hepatology.

[18]  L. Márk,et al.  Mass Spectrometry-Based Salivary Proteomics for the Discovery of Head and Neck Squamous Cell Carcinoma , 2012, Pathology & Oncology Research.

[19]  K. T. Patton,et al.  Decreased annexin I expression in prostatic adenocarcinoma and in high‐grade prostatic intraepithelial neoplasia , 2005, Histopathology.

[20]  J. Turnay,et al.  Differentiation of human colon adenocarcinoma cells alters the expression and intracellular localization of annexins A1, A2, and A5 , 2005, Journal of cellular biochemistry.

[21]  Yuanbo Kou,et al.  Annexin A1 mediates the anti‐adhesive effects of dexamethasone during the cell–cell interaction between the all‐trans retinoic acid‐treated acute promyelocytic leukemic cells and endothelial cells , 2013 .

[22]  Zhuchu Chen,et al.  Identification of Novel Nasopharyngeal Carcinoma Biomarkers by Laser Capture Microdissection and Proteomic Analysis , 2008, Clinical Cancer Research.

[23]  S. Leow,et al.  Annexin-1 interacts with NEMO and RIP1 to constitutively activate IKK complex and NF-κB: implication in breast cancer metastasis , 2011, Oncogene.

[24]  Steve Goodison,et al.  Proteomic profiling identifies breast tumor metastasis‐associated factors in an isogenic model , 2007, Proteomics.

[25]  Keli Ou,et al.  Novel breast cancer biomarkers identified by integrative proteomic and gene expression mapping. , 2008, Journal of proteome research.

[26]  X. Yang,et al.  Decreased expression of Annexin A1 correlates with pathologic differentiation grade in oral squamous cell carcinoma. , 2008, Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology.

[27]  Yankai Xia,et al.  Overexpression of annexin a1 induced by terephthalic acid calculi in rat bladder cancer , 2007, Proteomics.

[28]  José Vassallo,et al.  Overexpression of ANXA1 in Penile Carcinomas Positive for High-Risk HPVs , 2013, PloS one.

[29]  A. Pinchera,et al.  Fine-needle aspiration of thyroid nodules: proteomic analysis to identify cancer biomarkers. , 2008, Journal of proteome research.

[30]  Sung-Wuk Jang,et al.  The role of annexin A1 in expression of matrix metalloproteinase-9 and invasion of breast cancer cells. , 2012, Biochemical and biophysical research communications.

[31]  D. Noh,et al.  Clinical Significance of Annexin A1 Expression in Breast Cancer , 2011, Journal of breast cancer.

[32]  Ming-Rong Wang,et al.  Three isoforms of annexin I are preferentially expressed in normal esophageal epithelia but down-regulated in esophageal squamous cell carcinomas , 2002, Oncogene.

[33]  S. Ryozawa,et al.  Proteomic differential display analysis for TS-1-resistant and -sensitive pancreatic cancer cells using two-dimensional gel electrophoresis and mass spectrometry. , 2011, Anticancer research.

[34]  G. Stassi,et al.  Annexin-1 downregulation in thyroid cancer correlates to the degree of tumour differentiation , 2006, Cancer biology & therapy.

[35]  S. Mussunoor,et al.  The role of annexins in tumour development and progression , 2008, The Journal of pathology.

[36]  Sylvia E. Le Dévédec,et al.  Annexin A1 regulates TGF-β signaling and promotes metastasis formation of basal-like breast cancer cells , 2010, Proceedings of the National Academy of Sciences.

[37]  F. D’Acquisto,et al.  Annexin A1 and glucocorticoids as effectors of the resolution of inflammation , 2009, Nature Reviews Immunology.

[38]  Li‐yu Lee,et al.  Identification of differential gene expression between intestinal and diffuse gastric cancer using cDNA microarray. , 2006, Oncology reports.

[39]  K. Kumamoto,et al.  Up-regulated Annexin A1 expression in gastrointestinal cancer is associated with cancer invasion and lymph node metastasis. , 2011, Experimental and therapeutic medicine.

[40]  D. Ornstein,et al.  The impact of altered annexin I protein levels on apoptosis and signal transduction pathways in prostate cancer cells , 2006, The Prostate.

[41]  J. Vishwanatha,et al.  Absence of annexin I expression in B-cell non-Hodgkin's lymphomas and cell lines , 2004, BMC Cancer.

[42]  B. Zhu,et al.  Identification of Cervical Cancer Proteins Associated With Treatment With Paclitaxel and Cisplatin in Patients , 2011, International Journal of Gynecologic Cancer.

[43]  David Chia,et al.  Decreased expression of annexin A1 is correlated with breast cancer development and progression as determined by a tissue microarray analysis. , 2006, Human pathology.

[44]  P. Wong,et al.  Eurycomanone suppresses expression of lung cancer cell tumor markers, prohibitin, annexin 1 and endoplasmic reticulum protein 28. , 2012, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[45]  D. Ornstein,et al.  Dysregulation of annexin I protein expression in high-grade prostatic intraepithelial neoplasia and prostate cancer. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[46]  Yu Jin,et al.  Green tea induces annexin-I expression in human lung adenocarcinoma A549 cells: involvement of annexin-I in actin remodeling , 2007, Laboratory Investigation.

[47]  T. Deguchi,et al.  A Comparative Study of Protein Profiling by Proteomic Analysis in Camptothecin-Resistant PC3 and Camptothecin-Sensitive LNCaP Human Prostate Cancer Cells , 2006, Urologia Internationalis.

[48]  P R Taylor,et al.  Loss of annexin 1 correlates with early onset of tumorigenesis in esophageal and prostate carcinoma. , 2000, Cancer research.

[49]  H. Beug,et al.  Annexin A1 attenuates EMT and metastatic potential in breast cancer , 2010, EMBO molecular medicine.

[50]  G. Murray,et al.  Characterisation and protein expression profiling of annexins in colorectal cancer , 2007, British Journal of Cancer.

[51]  M. Fresno,et al.  Down-regulation of annexin A1 and A2 protein expression in intestinal-type sinonasal adenocarcinomas. , 2011, Human pathology.

[52]  Alice Lau,et al.  Loss of annexin A1 disrupts normal prostate glandular structure by inducing autocrine IL-6 signaling. , 2009, Carcinogenesis.

[53]  Manuel D. Díaz-Muñoz,et al.  A role for stroma-derived annexin A1 as mediator in the control of genetic susceptibility to T-cell lymphoblastic malignancies through prostaglandin E2 secretion. , 2009, Cancer Research.

[54]  E. Tajara,et al.  Annexin 1: Differential expression in tumor and mast cells in human larynx cancer , 2007, International journal of cancer.

[55]  Peng-Fei Zhang,et al.  Identification of annexin A1 as a proinvasive and prognostic factor for lung adenocarcinoma , 2011, Clinical & Experimental Metastasis.

[56]  N. Xu,et al.  A proteomic investigation into a human gastric cancer cell line BGC823 treated with diallyl trisulfide. , 2006, Carcinogenesis.

[57]  Peng-Yuan Yang,et al.  Identification and analysis of altered α1,6‐fucosylated glycoproteins associated with hepatocellular carcinoma metastasis , 2006 .

[58]  Ying Wang,et al.  Annexin-I expression modulates drug resistance in tumor cells. , 2004, Biochemical and biophysical research communications.

[59]  O. Krakovska,et al.  Identification of Novel Molecular Targets for Endometrial Cancer Using a Drill-Down LC-MS/MS Approach with iTRAQ , 2011, PloS one.

[60]  M. Toth,et al.  Elevated Levels of Annexin I Protein in vitro and in vivo in Rat and Human Mammary Adenocarcinoma , 1998, Clinical & Experimental Metastasis.

[61]  G Parmigiani,et al.  Androgen-induced programs for prostate epithelial growth and invasion arise in embryogenesis and are reactivated in cancer , 2008, Oncogene.

[62]  J. Turnay,et al.  Upregulation of Annexin A1 Expression by Butyrate in Human Colon Adenocarcinoma Cells: Role of p53, NF-Y, and p38 Mitogen-Activated Protein Kinase , 2008, Molecular and Cellular Biology.

[63]  X. Xu,et al.  Increased expression of annexin A1 is correlated with K-ras mutation in colorectal cancer. , 2010, The Tohoku journal of experimental medicine.

[64]  H. An,et al.  Proteomic identification of paclitaxel-resistance associated hnRNP A2 and GDI 2 proteins in human ovarian cancer cells. , 2010, Journal of proteome research.

[65]  S. Venz,et al.  Expression of annexin AI in conventional renal cell carcinoma (CRCC) correlates with tumour stage, Fuhrman grade, amount of eosinophilic cells and clinical outcome. , 2007, Histology and histopathology.

[66]  N. Wu,et al.  The role of annexin A3 playing in cancers , 2013, Clinical and Translational Oncology.

[67]  Concepcion R. Diaz-Arrastia,et al.  Implications of tyrosine phosphoproteomics in cervical carcinogenesis , 2008, Journal of carcinogenesis.

[68]  J. Rodrigo,et al.  Annexin A1 down-regulation in head and neck cancer is associated with epithelial differentiation status. , 2004, The American journal of pathology.

[69]  R. Layfield,et al.  Annexins in human breast cancer: Possible predictors of pathological response to neoadjuvant chemotherapy. , 2009, European journal of cancer.

[70]  S. Zucoloto,et al.  Myenteric denervation in gastric carcinogenesis: differential modulation of nitric oxide and annexin-A1. , 2013, International journal of clinical and experimental pathology.

[71]  B. Fontanella,et al.  Histone deacetylase inhibitor FR235222 sensitizes human prostate adenocarcinoma cells to apoptosis through up-regulation of Annexin A1. , 2010, Cancer letters.

[72]  M. Hande,et al.  Annexin-1 protects MCF7 breast cancer cells against heat-induced growth arrest and DNA damage. , 2010, Cancer letters.

[73]  V. Gerke,et al.  Structural basis of the Ca(2+)-dependent association between S100C (S100A11) and its target, the N-terminal part of annexin I. , 2000, Structure.

[74]  Katrin Trautmann,et al.  Comparative analysis of annexin-1 in neuroepithelial tumors shows altered expression with the grade of malignancy but is not associated with survival , 2009, Modern Pathology.

[75]  S. Marullo,et al.  A novel calcium‐dependent proapoptotic effect of annexin 1 on human neutrophils , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[76]  A. Karkhane,et al.  Proteomics of a new esophageal cancer cell line established from Persian patient. , 2012, Gene.

[77]  S. Baldus,et al.  Differential expression proteomics of human colorectal cancer based on a syngeneic cellular model for the progression of adenoma to carcinoma , 2010, Proteomics.

[78]  Chuanbing Shi,et al.  Up-regulation of hnRNP A1, Ezrin, tubulin β-2C and Annexin A1 in sentinel lymph nodes of colorectal cancer. , 2010, World journal of gastroenterology.

[79]  S. Zeng,et al.  Involvement of annexin A1 in multidrug resistance of K562/ADR cells identified by the proteomic study. , 2009, Omics : a journal of integrative biology.

[80]  T. Putti,et al.  Annexin-1 Regulates Growth Arrest Induced by High Levels of Estrogen in MCF-7 Breast Cancer Cells , 2009, Molecular Cancer Research.

[81]  H. Aburatani,et al.  Differential gene expression profiles of scirrhous gastric cancer cells with high metastatic potential to peritoneum or lymph nodes. , 2001, Cancer research.

[82]  D. Ornstein,et al.  Expression of annexin I, II and VII proteins in androgen stimulated and recurrent prostate cancer. , 2004, Journal of Urology.

[83]  M. Perretti,et al.  Annexin I Regulates SKCO-15 Cell Invasion by Signaling through Formyl Peptide Receptors* , 2006, Journal of Biological Chemistry.

[84]  G. Chang,et al.  Annexin A1 expression and its prognostic significance in human breast cancer. , 2010, Neoplasma.

[85]  K. Nan,et al.  Proteome analysis of the effects of sorafenib on human hepatocellular carcinoma cell line HepG2 , 2012, Medical Oncology.

[86]  J. Rao,et al.  Annexin‐I as a potential target for green tea extract induced actin remodeling , 2007, International journal of cancer.

[87]  G. Casey,et al.  Identification of metastasis-associated proteins through protein analysis of metastatic MDA-MB-435 and metastasis-suppressed BRMS1 transfected-MDA-MB-435 cells , 2004, Clinical & Experimental Metastasis.

[88]  Y. Yang,et al.  Decreased Expression of Annexin A1 during the Progression of Cervical Neoplasia , 2008, The Journal of international medical research.

[89]  Xiaohang Zhao,et al.  Translocation of annexin I from cellular membrane to the nuclear membrane in human esophageal squamous cell carcinoma. , 2003, World journal of gastroenterology.

[90]  D. Wang,et al.  Annexin-1 Downregulation Is Associated with Clinical Outcome in Chinese Patients with Hilar Cholangiocarcinoma , 2010, European Surgical Research.

[91]  Li Mao,et al.  Identification and validation of metastasis-associated proteins in head and neck cancer cell lines by two-dimensional electrophoresis and mass spectrometry , 2004, Clinical & Experimental Metastasis.

[92]  J. Clifton,et al.  Identification of members of the annexin family in the detergent-insoluble fraction of rat Morris hepatoma plasma membranes. , 2006, Journal of chromatography. A.

[93]  Zhuchu Chen,et al.  Preliminary proteomic analysis of indomethacin's effect on tumor transplanted with colorectal cancer cell in nude mice. , 2006, Journal of biochemistry and molecular biology.

[94]  K. Uzawa,et al.  Down-regulation of plasma membranous Annexin A1 protein expression in premalignant and malignant lesions of the oral cavity: correlation with epithelial differentiation , 2009, Journal of Cancer Research and Clinical Oncology.

[95]  A. Moser,et al.  The role of peroxisomal ABC transporters in the mouse adrenal gland: the loss of Abcd2 (ALDR), Not Abcd1 (ALD), causes oxidative damage , 2007, Laboratory Investigation.

[96]  A. Rashid,et al.  MicroRNA-196a targets annexin A1: a microRNA-mediated mechanism of annexin A1 downregulation in cancers , 2008, Oncogene.

[97]  Fang Liu,et al.  Overexpression of annexin 1 in pancreatic cancer and its clinical significance. , 2004, World journal of gastroenterology.

[98]  F. Kokocinski,et al.  Identification of novel tumour-associated genes differentially expressed in the process of squamous cell cancer development , 2006, Oncogene.

[99]  Katia Basso,et al.  Simple diagnostic assay for hairy cell leukaemia by immunocytochemical detection of annexin A1 (ANXA1) , 2004, The Lancet.

[100]  A. Tosco,et al.  Effects of FR235222, a novel HDAC inhibitor, in proliferation and apoptosis of human leukaemia cell lines: role of annexin A1. , 2008, European journal of cancer.

[101]  K. Uzawa,et al.  Identification of differentially expressed proteins in oral squamous cell carcinoma using a global proteomic approach. , 2005, International journal of oncology.

[102]  M. Sakaguchi,et al.  Truncation of Annexin A1 Is a Regulatory Lever for Linking Epidermal Growth Factor Signaling with Cytosolic Phospholipase A2 in Normal and Malignant Squamous Epithelial Cells* , 2007, Journal of Biological Chemistry.

[103]  M. Henry,et al.  Proteomic analysis of multidrug‐resistance mechanisms in adriamycin‐resistant variants of DLKP, a squamous lung cancer cell line , 2009, Proteomics.

[104]  U. Rescher,et al.  Disruption of the annexin A1/S100A11 complex increases the migration and clonogenic growth by dysregulating epithelial growth factor (EGF) signaling. , 2013, Biochimica et biophysica acta.

[105]  Shazib Pervaiz,et al.  Annexin 1: the new face of an old molecule , 2007, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[106]  Ting-feng Wu,et al.  Search for the tumor‐related proteins of transition cell carcinoma in Taiwan by proteomic analysis , 2006, Proteomics.

[107]  Ting-feng Wu,et al.  Annexin‐I overexpression is associated with tumour progression and independently predicts inferior disease‐specific and metastasis‐free survival in urinary bladder urothelial carcinoma , 2010, Pathology.

[108]  Y. Wong,et al.  Decreased GRP78 protein expression is a potential prognostic marker of oral squamous cell carcinoma in Taiwan. , 2010, Journal of the Formosan Medical Association = Taiwan yi zhi.

[109]  Qiang Li,et al.  Tissue microarray analysis reveals strong clinical evidence for a close association between loss of annexin A1 expression and nodal metastasis in gastric cancer , 2008, Clinical & Experimental Metastasis.

[110]  J. Maublant,et al.  Proteomic studies of B16 lines: involvement of annexin A1 in melanoma dissemination. , 2009, Biochimica et biophysica acta.

[111]  Kazuyuki Nakamura,et al.  Identification of differentially expressed proteins in tumour necrosis factor-alpha-resistant and -sensitive rat hepatoma cells. , 2011, Anticancer research.

[112]  J. Chiu,et al.  GADD45α and annexin A1 are involved in the apoptosis of HL-60 induced by resveratrol. , 2011, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[113]  V. Gerke,et al.  A novel ligand of the formyl peptide receptor: annexin I regulates neutrophil extravasation by interacting with the FPR. , 2000, Molecular cell.

[114]  K. Monastyrskaya,et al.  The annexins: spatial and temporal coordination of signaling events during cellular stress , 2009, Cellular and Molecular Life Sciences.

[115]  Yun Wu,et al.  Loss of Annexin A1 Expression in Breast Cancer Progression , 2008, Applied immunohistochemistry & molecular morphology : AIMM.

[116]  B. Yi,et al.  Annexin A1 protein regulates the expression of PMVEC cytoskeletal proteins in CBDL rat serum-induced pulmonary microvascular remodeling , 2013, Journal of Translational Medicine.

[117]  Rong Biaoxue,et al.  Upregulation of Hsp90-beta and annexin A1 correlates with poor survival and lymphatic metastasis in lung cancer patients , 2012, Journal of experimental & clinical cancer research : CR.

[118]  F. D’Acquisto,et al.  Pro-inflammatory and pathogenic properties of Annexin-A1: the whole is greater than the sum of its parts. , 2013, Biochemical pharmacology.