SIP1 protein protects cells from DNA damage-induced apoptosis and has independent prognostic value in bladder cancer

• DOI: 10.1073/pnas.0902042106
• Publication Date: 2009-08-18T02:11:52Z
• Authors: A. Emre Sayan; Thomas R. Griffiths; Raj Pal; Gareth J. Browne; Andrew Ruddick; Tamer Yagci; Richard Edwards; Nick J. Mayer; Hasan Qazi; Sandeep Goyal; Serena Fernandez; Kees Straatman; George D. D. Jones; Karen J. Bowman; Alexandra Colquhoun; J. Kilian Mellon; Marina Kriajevska; Eugene Tulchinsky
• Keywords: Value (mathematics)

The epithelial-mesenchymal transition (EMT) contributes to cancer metastasis. Two ZEB family members, ZEB1 and ZEB2(SIP1), inhibit transcription of the E-cadherin gene induce EMT in vitro. However, their relevance human is insufficiently studied. Here, we performed a comparative study SIP1 proteins cell lines one form malignancy, carcinoma bladder. Whereas protein was expressed all E-cadherin-negative lines, being part responsible for high motility bladder cells, hardly ever detectable cells culture. represented an independent factor poor prognosis ( P = 0.005) series specimens obtained from patients treated with radiotherapy. In contrast, rarely tumor tissues; status did not correlate patients' survival. protected UV- cisplatin-induced apoptosis vitro but had no effect on level DNA damage. anti-apoptotic either cycle arrest or loss cell-cell adhesion associated reduced phosphorylation ATM/ATR targets UV-treated cells. prognostic value its role damage response establish link between genetic instability metastasis suggest potential importance this as therapeutic target. addition, conclude that nature pathway rather than deregulation per se critical progression disease