title: p130Cas controls the susceptibility of cancer cells to TGF-β-induced growth inhibition.
abstract: Transforming growth factor-beta (TGF-β) suppresses the initiation of tumorigenesis by causing arrest at the G1 phase of the cell cycle. The loss of the antiproliferative function of TGF-β is a hallmark of many cancers. Here we report that p130Cas plays a role in determining the cellular responsiveness to TGF-β-induced growth inhibition in some cancer cells. An analysis of the tyrosine phosphorylation levels of p130Cas revealed higher levels of phosphorylation in cancer cell lines (MCF7 and A375) than in corresponding normal cell lines (MCF10A and MEL-STV). In contrast to normal cells, the cancer cells showed resistance to not only TGF-β-induced Smad3 phosphorylation and p21 expression, but also growth inhibition. However, silencing p130Cas using siRNA was sufficient to restore Smad3 phosphorylation and p21 expression, as well as the susceptibility to TGF-β-induced growth inhibition. Interestingly, the stable overexpression of p130Cas accelerated TGF-β-induced epithelial-mesenchymal transition. Our results suggest that elevated expression and tyrosine phosphorylation of p130Cas contributes to the resistance to TGF-β-induced growth inhibition, and thus to the initiation and progression of human cancers that harbor an active integrin signal.
authors.affiliation: Department of Life Science, Bio Imaging and Cell Dynamics Research Center, Gwangju Institute of Science and Technology, Gwangju 500-712, South Korea.
authors.forename: Yong Seok
authors.initials: YS
authors.lastname: Kang
authors.forename: Da Eun
authors.initials: DE
authors.lastname: Jeong
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Lee
authors.forename: Woo Keun
authors.initials: WK
authors.lastname: Song
authors.forename: Wook
authors.initials: W
authors.lastname: Kim
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D050719:Crk-Associated Substrate Protein / Q000378:metabolism*; D004198:Disease Susceptibility; D006801:Humans; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: C493841:BCAR1 protein, human; D050719:Crk-Associated Substrate Protein; D016212:Transforming Growth Factor beta
keywords: Cancer; EMT; Smad; TGF-β; p130Cas