Basic Research - Cancer(구연) Oral Session 3 / Basic Research - Cancer (Ⅱ) (O-023) Rm.201 10월 30일(수) 14:00-15:00 c-Met activation leads to the establishment of a TGFβ-receptor regulatory network in bladder cancer progression 부산대학교 의과대학 비뇨의학과교실¹ Institute of Molecular and Cell Biology,A*STAR, Singapore² Cancer Science Institute of Singapore,National University of Singapore³ 구자윤¹, Wen Jing Sim², Prasanna Vasudevan Iyengar³, Jean Paul Thiery², 김경환¹, 박지훈¹, 강병진¹, 박시균¹, 이권경¹, 하홍구¹ Treatment of muscle invasive bladder cancer remains a major clinical challenge. Aberrant HGF/cMET upregulation and activation is frequently observed in bladder cancer correlating with cancer progression and invasion.However, the mechanisms underlying HGF/cMET mediated invasion in bladder cancer remains unknown. We demonstrate that HGF stimulates TGFβ signalling through c-SRC mediated phosphorylation of SMURF2 resulting in loss of SMAD7 binding and enhanced SMURF2 C2HECT interaction, inhibiting SMURF2 and enhancing TGFβ receptor stabilization.This upregulation of the TGFβ pathway by HGF leads to TGFβ mediated EMT and invasion. In vivo we show that TGFβ receptor inhibition prevents bladder cancer invasion. Furthermore, we make a rationale for the use of combinatorial TGFβ and MEK inhibitors for treatment of high-grade non-muscle-invasive bladder cancers. keywords : Bladder cancer invasion, TGFβ, c-MET