Potential roles for prions and protein-only inheritance in cancer

Inherited mutations are known to cause familial cancers. However, the cause of sporadic cancers, which likely represent the majority of cancers, is yet to be elucidated. Sporadic cancers contain somatic mutations (including oncogenic mutations); however, the origin of these mutations is unclear. An intriguing possibility is that a stable alteration occurs in somatic cells prior to oncogenic mutations and promotes the subsequent accumulation of oncogenic mutations. This review explores the possible role of prions and protein-only inheritance in cancer. Genetic studies using lower eukaryotes, primarily yeast, have identified a large number of proteins as prions that confer dominant phenotypes with cytoplasmic (non-Mendelian) inheritance. Many of these have mammalian functional homologs. The human prion protein (PrP) is known to cause neurodegenerative diseases and has now been found to be upregulated in multiple cancers. PrP expression in cancer cells contributes to cancer progression and resistance to various cancer therapies. Epigenetic changes in the gene expression and hyperactivation of MAP kinase signaling, processes that in lower eukaryotes are affected by prions, play important roles in oncogenesis in humans. Prion phenomena in yeast appear to be influenced by stresses, and there is considerable evidence of the association of some amyloids with biologically positive functions. This suggests that if protein-only somatic inheritance exists in mammalian cells, it might contribute to cancer phenotypes. Here, we highlight evidence in the literature for an involvement of prion or prion-like mechanisms in cancer and how they may in the future be viewed as diagnostic markers and potential therapeutic targets.

[1]  W. Xin,et al.  The fatal attraction between pro-prion and filamin A: prion as a marker in human cancers. , 2010, Biomarkers in medicine.

[2]  Jonathan S Weissman,et al.  Dissection and Design of Yeast Prions , 2004, PLoS biology.

[3]  Y. Mishima,et al.  INCREASED IN VITRO RADIO‐SENSITIVITY OF MALGNANT MELANOMA INDUCED BY THE IN VIVO ADMINISTRATION OF CHLORPROMAZINE , 1972, The British journal of dermatology.

[4]  J. Richter,et al.  CPEB regulation of human cellular senescence, energy metabolism, and p53 mRNA translation. , 2008, Genes & development.

[5]  E. Triphosphat,et al.  FEBS Letters , 1987, FEBS Letters.

[6]  A. Pesce,et al.  The (1-63) region of the p53 transactivation domain aggregates in vitro into cytotoxic amyloid assemblies. , 2008, Biophysical journal.

[7]  Y. Cordeiro,et al.  Fibrillar aggregates of the tumor suppressor p53 core domain. , 2003, Biochemistry.

[8]  V. Coustou,et al.  The protein product of the het-s heterokaryon incompatibility gene of the fungus Podospora anserina behaves as a prion analog. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[9]  Thorsten Lührs,et al.  Correlation of structural elements and infectivity of the HET-s prion , 2005, Nature.

[10]  Eric R. Kandel,et al.  Aplysia CPEB Can Form Prion-like Multimers in Sensory Neurons that Contribute to Long-Term Facilitation , 2010, Cell.

[11]  B. Polić,et al.  Cellular and Molecular Life Sciences MULTI-AUTHOR REVIEW Regulation of immune cell function and differentiation , 2022 .

[12]  M. Tuite,et al.  Chaperoning prions: the cellular machinery for propagating an infectious protein? , 2005, BioEssays : news and reviews in molecular, cellular and developmental biology.

[13]  A. Lykkesfeldt,et al.  The antipsychotic drug chlorpromazine enhances the cytotoxic effect of tamoxifen in tamoxifen-sensitive and tamoxifen-resistant human breast cancer cells , 2009, Anti-cancer drugs.

[14]  S. Kicka,et al.  A mitotically inheritable unit containing a MAP kinase module , 2006, Proceedings of the National Academy of Sciences.

[15]  C. Cullin,et al.  The yeast prion [URE3] can be greatly induced by a functional mutated URE2 allele , 2000, The EMBO journal.

[16]  D. Dormont Prion diseases: pathogenesis and public health concerns , 2002, FEBS letters.

[17]  Haifeng Jin,et al.  Cellular prion protein promotes invasion and metastasis of gastric cancer , 2006, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[18]  S. Fulda Tumor resistance to apoptosis , 2009, International journal of cancer.

[19]  Y. Chernoff,et al.  Destabilization and recovery of a yeast prion after mild heat shock. , 2011, Journal of molecular biology.

[20]  S. Lindquist,et al.  Prion Switching in Response to Environmental Stress , 2008, PLoS biology.

[21]  S. Lindquist,et al.  A heritable switch in carbon source utilization driven by an unusual yeast prion. , 2009, Genes & development.

[22]  S. Liebman,et al.  Prions Affect the Appearance of Other Prions The Story of [PIN+] , 2001, Cell.

[23]  S. Liebman,et al.  "Prion-proof" for [PIN+]: infection with in vitro-made amyloid aggregates of Rnq1p-(132-405) induces [PIN+]. , 2007, Journal of molecular biology.

[24]  H. Xiang,et al.  Human alphaA- and alphaB-crystallins bind to Bax and Bcl-X(S) to sequester their translocation during staurosporine-induced apoptosis. , 2004, Cell death and differentiation.

[25]  Gang Chen,et al.  Activation of PI3K/Akt/IKK-α/NF-κB signaling pathway is required for the apoptosis-evasion in human salivary adenoid cystic carcinoma: its inhibition by quercetin , 2010, Apoptosis.

[26]  D. Fan,et al.  Inhibition of PI3K/Akt partially leads to the inhibition of PrPC‐induced drug resistance in gastric cancer cells , 2009, The FEBS journal.

[27]  F. Lacroute Non-Mendelian Mutation Allowing Ureidosuccinic Acid Uptake in Yeast , 1971, Journal of bacteriology.

[28]  C. Kurschner,et al.  Analysis of interaction sites in homo- and heteromeric complexes containing Bcl-2 family members and the cellular prion protein. , 1996, Brain research. Molecular brain research.

[29]  C. Harris,et al.  p53 tumor suppressor gene: from the basic research laboratory to the clinic--an abridged historical perspective. , 1996, Carcinogenesis.

[30]  C. Gabus,et al.  The Prion Protein Has RNA Binding and Chaperoning Properties Characteristic of Nucleocapsid Protein NCp7 of HIV-1* , 2001, The Journal of Biological Chemistry.

[31]  M. Kao,et al.  Creutzfeldt-Jakob disease: heat shock protein 70 mRNA levels in mononuclear blood cells and clinical study , 2000, Journal of Neurology.

[32]  K. Volkov,et al.  Non-Mendelian determinant [ISP+] in yeast is a nuclear-residing prion form of the global transcriptional regulator Sfp1 , 2010, Proceedings of the National Academy of Sciences.

[33]  Xin Wang,et al.  Cellular prion protein promotes proliferation and G1/S transition of human gastric cancer cells SGC7901 and AGS , 2007, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[34]  M. Gottesman,et al.  The molecular basis of multidrug resistance in cancer: The early years of P‐glycoprotein research , 2006, FEBS letters.

[35]  R. Wickner,et al.  Yeast prions [URE3] and [PSI+] are diseases. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[36]  F. Checler,et al.  The α-Secretase-derived N-terminal Product of Cellular Prion, N1, Displays Neuroprotective Function in Vitro and in Vivo* , 2009, The Journal of Biological Chemistry.

[37]  J. Jardillier,et al.  Expression of mdr1 gene in human breast primary tumors and metastases , 2004, Breast Cancer Research and Treatment.

[38]  Y. Chernoff,et al.  Evidence for a Protein Mutator in Yeast: Role of the Hsp70-Related Chaperone Ssb in Formation, Stability, and Toxicity of the [PSI] Prion , 1999, Molecular and Cellular Biology.

[39]  D. Harris,et al.  A prion protein cycles between the cell surface and an endocytic compartment in cultured neuroblastoma cells. , 1993, The Journal of biological chemistry.

[40]  N. Makarava,et al.  The Same Primary Structure of the Prion Protein Yields Two Distinct Self-propagating States* , 2008, Journal of Biological Chemistry.

[41]  S. Lindquist,et al.  Protein-only mechanism induces self-perpetuating changes in the activity of neuronal Aplysia cytoplasmic polyadenylation element binding protein (CPEB) , 2011, Proceedings of the National Academy of Sciences.

[42]  S. Duvezin-Caubet,et al.  Amyloid aggregates of the HET-s prion protein are infectious , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[43]  F E Cohen,et al.  Acridine and phenothiazine derivatives as pharmacotherapeutics for prion disease , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[44]  G. Shapiro,et al.  Development of Phosphoinositide-3 Kinase Pathway Inhibitors for Advanced Cancer , 2010, Current oncology reports.

[45]  A. Aguzzi,et al.  Mice devoid of PrP are resistant to scrapie , 1993, Cell.

[46]  J. Milner,et al.  Cotranslation of activated mutant p53 with wild type drives the wild-type p53 protein into the mutant conformation , 1991, Cell.

[47]  J. Cheng,et al.  Apoptosis of metastatic prostate cancer cells by a combination of cyclin-dependent kinase and AKT inhibitors. , 2009, The international journal of biochemistry & cell biology.

[48]  Haijing Yu,et al.  Newly identified prion linked to the chromatin-remodeling factor Swi1 in Saccharomyces cerevisiae , 2008, Nature Genetics.

[49]  J. Ott,et al.  The p53MH algorithm and its application in detecting p53-responsive genes , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[50]  S. Prusiner,et al.  Resistance of Bovine Spongiform Encephalopathy (BSE) Prions to Inactivation , 2008, PLoS pathogens.

[51]  S. Liebman,et al.  Specificity of Prion Assembly in Vivo , 2004, Journal of Biological Chemistry.

[52]  R. Wickner,et al.  [URE3] as an altered URE2 protein: evidence for a prion analog in Saccharomyces cerevisiae. , 1994, Science.

[53]  E. Kandel,et al.  A Neuronal Isoform of the Aplysia CPEB Has Prion-Like Properties , 2003, Cell.

[54]  S. Prusiner,et al.  Conversion of truncated and elongated prion proteins into the scrapie isoform in cultured cells. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[55]  J. Xiang,et al.  Epigenetic transfer of metastatic activity by uptake of highly metastatic B16 melanoma cell-released exosomes. , 2006, Experimental oncology.

[56]  J. Royds,et al.  Enhanced anti‐cancer effect of a phosphatidylinositol‐3 kinase inhibitor and doxorubicin on human breast epithelial cell lines with different p53 and oestrogen receptor status , 2008, International journal of cancer.

[57]  M. Mathieu,et al.  Efficacy of adjuvant chemotherapy according to Prion protein expression in patients with estrogen receptor-negative breast cancer. , 2007, Annals of oncology : official journal of the European Society for Medical Oncology.

[58]  Y. Chernoff,et al.  Genetic and environmental factors affecting the de novo appearance of the [PSI+] prion in Saccharomyces cerevisiae. , 1997, Genetics.

[59]  Mrc Prion Kuru in the 21st century-an acquired human prion disease with very long incubation periods , 2006 .

[60]  P. Wust,et al.  The cellular and molecular basis of hyperthermia. , 2002, Critical reviews in oncology/hematology.

[61]  John Collinge,et al.  Kuru in the 21st century—an acquired human prion disease with very long incubation periods , 2006, The Lancet.

[62]  R. Ribeiro,et al.  Reversible amyloid formation by the p53 tetramerization domain and a cancer-associated mutant. , 2003, Journal of molecular biology.

[63]  Y. Chernoff,et al.  Modulation of Prion Formation, Aggregation, and Toxicity by the Actin Cytoskeleton in Yeast , 2006, Molecular and Cellular Biology.

[64]  B. Chesebro,et al.  N-terminal Truncation of Prion Protein Affects Both Formation and Conformation of Abnormal Protease-resistant Prion Protein Generatedin Vitro * , 2001, The Journal of Biological Chemistry.

[65]  Y. Chernoff,et al.  Sequence specificity and fidelity of prion transmission in yeast. , 2011, Seminars in cell & developmental biology.

[66]  M. Tuite,et al.  Oligopeptide repeats in the yeast protein Sup35p stabilize intermolecular prion interactions , 2001, The EMBO journal.

[67]  U. Baxa,et al.  Prion generation in vitro: amyloid of Ure2p is infectious , 2005, The EMBO journal.

[68]  J. Weissman,et al.  A census of glutamine/asparagine-rich regions: implications for their conserved function and the prediction of novel prions. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[69]  S. Müller,et al.  Prion variant maintained only at high levels of the Hsp104 disaggregase , 2005, Current Genetics.

[70]  S. Chouaib,et al.  Silencing of prion protein sensitizes breast adriamycin-resistant carcinoma cells to TRAIL-mediated cell death. , 2007, Cancer research.

[71]  Y. Chernoff,et al.  An antiprion effect of the anticytoskeletal drug latrunculin A in yeast. , 2001, Gene expression.

[72]  D. El-Ashry,et al.  ER Re-expression and Re-sensitization to Endocrine Therapies in ER-negative Breast Cancers , 2009, Journal of Mammary Gland Biology and Neoplasia.

[73]  Kohei Uosaki,et al.  Unfolding, aggregation, and amyloid formation by the tetramerization domain from mutant p53 associated with lung cancer. , 2006, Biochemistry.

[74]  Luquan Wang,et al.  Global transcriptional program of p53 target genes during the process of apoptosis and cell cycle progression , 2003, Oncogene.

[75]  S. Lindquist,et al.  Prion induction involves an ancient system for the sequestration of aggregated proteins and heritable changes in prion fragmentation , 2010, Proceedings of the National Academy of Sciences.

[76]  L. Meijer,et al.  Isolation of drugs active against mammalian prions using a yeast-based screening assay , 2003, Nature Biotechnology.

[77]  R. Wickner,et al.  Two Prion-Inducing Regions of Ure2p Are Nonoverlapping , 1999, Molecular and Cellular Biology.

[78]  D. Kocisko,et al.  Octapeptide repeat insertions increase the rate of protease‐resistant prion protein formation , 2006, Protein science : a publication of the Protein Society.

[79]  D. Alberts,et al.  Fundamentals of Cancer Prevention , 2005 .

[80]  Jonathan S. Weissman,et al.  The physical basis of how prion conformations determine strain phenotypes , 2006, Nature.

[81]  V. Schirrmacher,et al.  Shifts in tumor cell phenotypes induced by signals from the microenvironment. Relevance for the immunobiology of cancer metastasis. , 1980, Immunobiology.

[82]  A. Antonacopoulou,et al.  POLR2F, ATP6V0A1 and PRNP expression in colorectal cancer: new molecules with prognostic significance? , 2008, Anticancer research.

[83]  Elke S. Bergmann-Leitner,et al.  Editorial [Hot Topic: Anti-Cancer Drugs Executive Editor: Elke Bergmann-Leitner] , 2005 .

[84]  J. Buchner,et al.  The Prion Curing Agent Guanidinium Chloride Specifically Inhibits ATP Hydrolysis by Hsp104* , 2004, Journal of Biological Chemistry.

[85]  S. Prusiner,et al.  Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein , 1992, Nature.

[86]  S. Lindquist,et al.  Prion protein gene polymorphisms in Saccharomyces cerevisiae , 2003, Molecular microbiology.

[87]  A. D’Ambrogio,et al.  CPEB and two poly(A) polymerases control miR-122 stability and p53 mRNA translation , 2011, Nature.

[88]  S. Liebman,et al.  Dependence and independence of [PSI+] and [PIN+]: a two‐prion system in yeast? , 2000, The EMBO journal.

[89]  B. Caughey,et al.  Reversibility of Scrapie-associated Prion Protein Aggregation* , 2001, The Journal of Biological Chemistry.

[90]  Andrew F. Hill,et al.  Molecular analysis of prion strain variation and the aetiology of 'new variant' CJD , 1996, Nature.

[91]  D. Fan,et al.  Overexpression of PrPC and Its Antiapoptosis Function in Gastric Cancer , 2006, Tumor Biology.

[92]  R. Herbst,et al.  To kill a tumor cell: the potential of proapoptotic receptor agonists. , 2008, The Journal of clinical investigation.

[93]  S. Supattapone,et al.  RNA molecules stimulate prion protein conversion , 2003, Nature.

[94]  J. Shorter Emergence and natural selection of drug-resistant prions. , 2010, Molecular bioSystems.

[95]  B. Chesebro,et al.  Conversion of raft associated prion protein to the protease‐resistant state requires insertion of PrP‐res (PrPSc) into contiguous membranes , 2002, The EMBO journal.

[96]  Jin-Ming Yang,et al.  Up‐regulation of CD147 and matrix metalloproteinase‐2, ‐9 induced by P‐glycoprotein substrates in multidrug resistant breast cancer cells , 2007, Cancer science.

[97]  Y. Chernoff,et al.  Biological Roles of Prion Domains , 2007, Prion.

[98]  Stanley B. Prusiner,et al.  Nobel Lecture: Prions , 1998 .

[99]  S. Nonogaki,et al.  Prion protein ablation increases cellular aggregation and embolization contributing to mechanisms of metastasis , 2009, International journal of cancer.

[100]  I. Fidler,et al.  Tumor heterogeneity and the biology of cancer invasion and metastasis. , 1978, Cancer research.

[101]  S. Liebman,et al.  The yeast global transcriptional co-repressor protein Cyc8 can propagate as a prion , 2009, Nature Cell Biology.

[102]  S W Liebman,et al.  Role of the chaperone protein Hsp104 in propagation of the yeast prion-like factor [psi+]. , 1995, Science.

[103]  A. Papavassiliou,et al.  Prion protein expression and the M129V polymorphism of the PRNP gene in patients with colorectal cancer , 2010, Molecular carcinogenesis.

[104]  V. Ling,et al.  Metastatic variants are generated spontaneously at a high rate in mouse KHT tumor. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[105]  Samuel Arrabal,et al.  Prion Protein Prevents Human Breast Carcinoma Cell Line from Tumor Necrosis Factor α-Induced Cell Death , 2004, Cancer Research.

[106]  Y. Chernoff,et al.  Genetic study of interactions between the cytoskeletal assembly protein sla1 and prion-forming domain of the release factor Sup35 (eRF3) in Saccharomyces cerevisiae. , 1999, Genetics.

[107]  D. Hanahan,et al.  Hallmarks of Cancer: The Next Generation , 2011, Cell.

[108]  J. McNally,et al.  Prion induction by the short-lived, stress-induced protein Lsb2 is regulated by ubiquitination and association with the actin cytoskeleton. , 2011, Molecular cell.

[109]  F. Checler,et al.  Overexpression of PrPc triggers caspase 3 activation: potentiation by proteasome inhibitors and blockade by anti‐PrP antibodies , 2002, Journal of neurochemistry.

[110]  Christopher G. Adda,et al.  Interaction of the Molecular Chaperone αB-Crystallin with α-Synuclein: Effects on Amyloid Fibril Formation and Chaperone Activity , 2004 .

[111]  B. Roberts,et al.  Heritable activity: a prion that propagates by covalent autoactivation. , 2003, Genes & development.

[112]  Y. Say,et al.  Resistance against apoptosis by the cellular prion protein is dependent on its glycosylation status in oral HSC-2 and colon LS 174T cancer cells. , 2011, Cancer letters.

[113]  P. Codogno,et al.  Prion protein: From physiology to cancer biology. , 2010, Cancer letters.

[114]  J. Collinge,et al.  Disease-related Prion Protein Forms Aggresomes in Neuronal Cells Leading to Caspase Activation and Apoptosis* , 2005, Journal of Biological Chemistry.

[115]  X. Guo,et al.  Role of PrPc Related to Apoptosis , 2006 .

[116]  S. Frank Age-specific incidence of inherited versus sporadic cancers: a test of the multistage theory of carcinogenesis. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[117]  J. Hescheler,et al.  Redox-regulation of intrinsic prion expression in multicellular prostate tumor spheroids. , 1999, Free radical biology & medicine.

[118]  Y. Chernoff,et al.  Genesis and variability of [PSI] prion factors in Saccharomyces cerevisiae. , 1996, Genetics.

[119]  Jung-Young Shin,et al.  LY294002 may overcome 5-FU resistance via down-regulation of activated p-AKT in Epstein-Barr virus-positive gastric cancer cells , 2010, BMC Cancer.

[120]  B. Turcq,et al.  Vegetative incompatibility in filamentous fungi: a roundabout way of understanding the phenomenon. , 2000, Research in microbiology.

[121]  Y. Chernoff Stress and prions: Lessons from the yeast model , 2007, FEBS letters.

[122]  Roger Cooke,et al.  Conformational variations in an infectious protein determine prion strain differences , 2004, Nature.

[123]  Y. Cordeiro,et al.  Ligand Binding and Hydration in Protein Misfolding: Insights from Studies of Prion and p53 Tumor Suppressor Proteins† , 2009, Accounts of chemical research.

[124]  F. Cohen,et al.  A Protease-Resistant 61-Residue Prion Peptide Causes Neurodegeneration in Transgenic Mice , 2001, Molecular and Cellular Biology.

[125]  T. Onodera,et al.  Molecular modulation of expression of prion protein by heat shock , 2002, Molecular Neurobiology.

[126]  G. Raposo,et al.  Exosomes: A Bubble Ride for Prions? , 2005, Traffic.

[127]  A. J. Clifford,et al.  BIOCHIMICA ET BIOPHYSICA ACTA , 2022 .

[128]  Y. Chernoff,et al.  Yeast prion protein derivative defective in aggregate shearing and production of new ‘seeds’ , 2001, The EMBO journal.

[129]  X. Roucou,et al.  A large ribonucleoprotein particle induced by cytoplasmic PrP shares striking similarities with the chromatoid body, an RNA granule predicted to function in posttranscriptional gene regulation. , 2009, Biochimica et biophysica acta.

[130]  M. Tuite,et al.  Prion Stability , 2007, Prion.

[131]  Y. Chernoff,et al.  Hsp104 and prion propagation. , 2009, Protein and peptide letters.

[132]  S. Lindquist,et al.  [PSI+]: an epigenetic modulator of translation termination efficiency. , 1999, Annual review of cell and developmental biology.

[133]  Rui Gong,et al.  Bovine PrPC directly interacts with αB‐crystalline , 2005 .

[134]  Erik Sahai,et al.  The actin cytoskeleton in cancer cell motility , 2009, Clinical & Experimental Metastasis.

[135]  C. Stackpole Generation of phenotypic diversity in the B16 mouse melanoma relative to spontaneous metastasis. , 1983, Cancer research.

[136]  E. Kremmer,et al.  The yeast Sup35NM domain propagates as a prion in mammalian cells , 2009, Proceedings of the National Academy of Sciences.

[137]  D. Fan,et al.  Overexpression and significance of prion protein in gastric cancer and multidrug‐resistant gastric carcinoma cell line SGC7901/ADR , 2005, International journal of cancer.

[138]  R. Wickner,et al.  Suicidal [PSI+] is a lethal yeast prion , 2011, Proceedings of the National Academy of Sciences.

[139]  J. Mcewan,et al.  Antibodies to Prion Protein Inhibit Human Colon Cancer Cell Growth , 2009, Tumor Biology.

[140]  B. Cox,et al.  Ψ, A cytoplasmic suppressor of super-suppressor in yeast , 1965, Heredity.

[141]  J. Gray,et al.  The genetics and genomics of cancer , 2003, Nature Genetics.

[142]  Acta Virologica , 1957, Nature.

[143]  H. Xiang,et al.  Human αA- and αB-crystallins bind to Bax and Bcl-XS to sequester their translocation during staurosporine-induced apoptosis , 2004, Cell Death and Differentiation.

[144]  S. Prusiner Novel proteinaceous infectious particles cause scrapie. , 1982, Science.

[145]  S. Lindquist,et al.  Epigenetics in the Extreme: Prions and the Inheritance of Environmentally Acquired Traits , 2010, Science.

[146]  S. Batra,et al.  The small heat shock protein alphaA-crystallin is expressed in pancreas and acts as a negative regulator of carcinogenesis. , 2010, Biochimica et biophysica acta.

[147]  Y. Chernoff,et al.  Evolutionary conservation of prion‐forming abilities of the yeast Sup35 protein , 2000, Molecular microbiology.

[148]  I. Baskakov,et al.  Unraveling prion structures and biological functions , 2006, Genome Biology.

[149]  M. Tsao,et al.  Inhibition of phosphatidylinositide 3-kinase enhances gemcitabine-induced apoptosis in human pancreatic cancer cells. , 2000, Cancer research.

[150]  M. Tuite,et al.  Prions remodel gene expression in yeast , 2009, Nature Cell Biology.

[151]  W. Hait,et al.  Overexpression of extracellular matrix metalloproteinase inducer in multidrug resistant cancer cells. , 2003, Molecular cancer research : MCR.

[152]  X. Roucou,et al.  Cellular prion protein inhibits proapoptotic Bax conformational change in human neurons and in breast carcinoma MCF-7 cells , 2005, Cell Death and Differentiation.

[153]  Shaoman Yin,et al.  Binding of pro-prion to filamin A disrupts cytoskeleton and correlates with poor prognosis in pancreatic cancer. , 2009, The Journal of clinical investigation.

[154]  C. Kurschner,et al.  The cellular prion protein (PrP) selectively binds to Bcl-2 in the yeast two-hybrid system. , 1995, Brain research. Molecular brain research.

[155]  Haiyong Han,et al.  Identification of differentially expressed genes in pancreatic cancer cells using cDNA microarray. , 2002, Cancer research.

[156]  Susan Lindquist,et al.  Prions, protein homeostasis, and phenotypic diversity. , 2010, Trends in cell biology.

[157]  P. Armitage,et al.  The age distribution of cancer and a multi-stage theory of carcinogenesis , 1954, British Journal of Cancer.

[158]  G. Dewson,et al.  Mechanisms by which Bak and Bax permeabilise mitochondria during apoptosis , 2009, Journal of Cell Science.

[159]  O. King,et al.  A Systematic Survey Identifies Prions and Illuminates Sequence Features of Prionogenic Proteins , 2009, Cell.

[160]  R. Duan,et al.  LY294002 enhances boswellic acid-induced apoptosis in colon cancer cells. , 2009, Anticancer research.

[161]  Roland Winter,et al.  The amino-terminal PrP domain is crucial to modulate prion misfolding and aggregation. , 2005, Biophysical journal.

[162]  F. Tang,et al.  The role of P-glycoprotein/cellular prion protein interaction in multidrug-resistant breast cancer cells treated with paclitaxel , 2009, Cellular and Molecular Life Sciences.

[163]  Andrew W. Murray,et al.  Estimating the Per-Base-Pair Mutation Rate in the Yeast Saccharomyces cerevisiae , 2008, Genetics.

[164]  F. Chen,et al.  The Small Heat Shock Protein αB-Crystallin Negatively Regulates Cytochrome c- and Caspase-8-dependent Activation of Caspase-3 by Inhibiting Its Autoproteolytic Maturation* , 2001, The Journal of Biological Chemistry.

[165]  R. Wickner,et al.  Yeast Prions , 2007, Prion.

[166]  M. Maddelein,et al.  A non-Q/N-rich prion domain of a foreign prion, [Het-s], can propagate as a prion in yeast. , 2007, Molecular cell.

[167]  P. Tien,et al.  Bovine PrPC directly interacts with alphaB-crystalline. , 2005, FEBS letters.

[168]  H. True,et al.  A yeast prion provides a mechanism for genetic variation and phenotypic diversity , 2000, Nature.

[169]  J. Lazo,et al.  Expression of the c-Ha-ras oncogene in mouse NIH 3T3 cells induces resistance to cisplatin. , 1991, Cancer research.

[170]  K. Wilkinson,et al.  Effects of Ubiquitin System Alterations on the Formation and Loss of a Yeast Prion*♦ , 2007, Journal of Biological Chemistry.