CAS promotes invasiveness of Src-transformed cells

被引:75
作者
Brábek, J
Constancio, BS
Shin, NY
Pozzi, A
Weaver, AM
Hanks, SK [1 ]
机构
[1] Vanderbilt Univ, Sch Med, Dept Cell & Dev Biol, Nashville, TN 37212 USA
[2] Vanderbilt Univ, Sch Med, Dept Canc Biol, Nashville, TN 37212 USA
[3] Vanderbilt Univ, Sch Med, Dept Med Nephrol, Nashville, TN 37212 USA
[4] Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37212 USA
关键词
p130CAS; Src; cortactin; MMP-2; invasion; podosome;
D O I
10.1038/sj.onc.1207965
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
CAS ('Crk-associated substrate') is an Src substrate found at sites of integrin-mediated cell adhesion and linked to cell motility and survival. In this study, the involvement of CAS in oncogenic transformation was evaluated through analysis of mouse embryo fibroblast populations expressing an activated Src mutant, either in the presence or absence of CAS expression. CAS was not found to be a critical determinant of either Src-mediated morphologic transformation or anchorage-independent growth. However, CAS had a profound effect on other aspects of oncogenic Src function. CAS expression led to a substantial increase in the phosphotyrosine content of FAK and paxillin, supporting a role for CAS as a positive regulator of Src activity at integrin adhesion sites. Importantly, CAS expression resulted in a striking enhancement of the capacity of Src-transformed cells to invade through Matrigel. The increased invasiveness was associated with increased activation of matrix metalloproteinase MMP-2 and formation of large actin-rich podosomal aggregates appearing as ring and belt structures. Thus, elevated CAS-associated tyrosine phosphorylation signaling events occurring at sites of integrin-mediated cell adhesion can have a major role in the development of an invasive cell phenotype.
引用
收藏
页码:7406 / 7415
页数:10
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