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dc.contributor.authorSayan, A. E.en_US
dc.contributor.authorGriffiths, T. R.en_US
dc.contributor.authorPal, R.en_US
dc.contributor.authorBrowne G. J.en_US
dc.contributor.authorRuddick, A.en_US
dc.contributor.authorYagci, T.en_US
dc.contributor.authorEdwards, R.en_US
dc.contributor.authorMayer, N. J.en_US
dc.contributor.authorQazi, H.en_US
dc.contributor.authorGoyal, S.en_US
dc.contributor.authorFernandez, S.en_US
dc.contributor.authorStraatman, K.en_US
dc.contributor.authorJones G. D. D.en_US
dc.contributor.authorBowman, K. J.en_US
dc.contributor.authorColquhoun, A.en_US
dc.contributor.authorMellon, J. K.en_US
dc.contributor.authorKriajevska, M.en_US
dc.contributor.authorTulchinsky, E.en_US
dc.date.accessioned2016-02-08T10:02:48Z
dc.date.available2016-02-08T10:02:48Z
dc.date.issued2009en_US
dc.identifier.issn0027-8424
dc.identifier.urihttp://hdl.handle.net/11693/22640
dc.description.abstractThe epithelial-mesenchymal transition (EMT) contributes to cancer metastasis. Two ZEB family members, ZEB1 and ZEB2(SIP1), inhibit transcription of the E-cadherin gene and induce EMT in vitro. However, their relevance to human cancer is insufficiently studied. Here, we performed a comparative study of SIP1 and ZEB1 proteins in cancer cell lines and in one form of human malignancy, carcinoma of the bladder. Whereas ZEB1 protein was expressed in all E-cadherin-negative carcinoma cell lines, being in part responsible for the high motility of bladder cancer cells, SIP1 was hardly ever detectable in carcinoma cells in culture. However, SIP1 represented an independent factor of poor prognosis (P = 0.005) in a series of bladder cancer specimens obtained from patients treated with radiotherapy. In contrast, ZEB1 was rarely expressed in tumor tissues; and E-cadherin status did not correlate with the patients' survival. SIP1 protected cells from UV- and cisplatin-induced apoptosis in vitro but had no effect on the level of DNA damage. The anti-apoptotic effect of SIP1 was independent of either cell cycle arrest or loss of cell-cell adhesion and was associated with reduced phosphorylation of ATM/ATR targets in UV-treated cells. The prognostic value of SIP1 and its role in DNA damage response establish a link between genetic instability and metastasis and suggest a potential importance for this protein as a therapeutic target. In addition, we conclude that the nature of an EMT pathway rather than the deregulation of E-cadherin per se is critical for the progression of the disease and patients' survival.en_US
dc.language.isoEnglishen_US
dc.source.titleProceedings of the National Academy of Sciences of the United States of Americaen_US
dc.relation.isversionofhttp://dx.doi.org/10.1073/pnas.0902042106en_US
dc.subjectCisplatinen_US
dc.subjectDNAen_US
dc.subjectIron binding proteinen_US
dc.subjectSeleniumen_US
dc.subjectSip1 proteinen_US
dc.subjectTranscription factor Snailen_US
dc.subjectUnclassified drugen_US
dc.subjectUvomorulinen_US
dc.titleSIP1 protein protects cells from DNA damage-induced apoptosis and has independent prognostic value in bladder canceren_US
dc.typeArticleen_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.citation.spage14884en_US
dc.citation.epage14889en_US
dc.citation.volumeNumber106en_US
dc.citation.issueNumber35en_US
dc.identifier.doi10.1073/pnas.0902042106en_US
dc.publisherNational Academy of Sciencesen_US


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