Blockade of v‐Src‐stimulated tumor formation by the Src homology 3 domain of Crk‐associated substrate (Cas)

FEBS Letters

Chan, Po-Chao²  Huang, Chi-Hui²  Cheng, Chi-Hung⁴  Chen, Hsin-Ling²  Wung, Chiung-Wha³  Chen, Shu-Yi²  Yu, Kuo-Ching¹  Chen, Hong-Chen² 

[1] Department of Pathology, Taichung Veterans General Hospital, Taichung, Taiwan;Graduate Institute of Biomedical Sciences, National Chung Hsing University, 250 Kuo-Kuang road, Taichung 40227, Taiwan;Biotechnology Center, National Chung Hsing University, Taichung, Taiwan;Section of Nephrology, Taichung Veterans General Hospital, Taichung, Taiwan

关键词: Src;    Crk-associated substrate;    Src homology 3 domain;    Tumor;    Anoikis;    Invasion;    Cas;    Crk-associated substrate;    SH;    Src homology;    PI3K;    phosphatidylinositol 3-kinase;    FAK;    focal adhesion kinase;    HA;    hemagglutinin;    polyHEMA;    poly-hydroxyethylmethacrylate;    PYK2;    proline-rich tyrosine kinase 2;    MMP;    matrix metalloproteinase;   

DOI  :  10.1016/S0014-5793(03)01501-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Crk-associated substrate (Cas) is highly phosphorylated by v-Src and plays a critical role in v-Src-induced cell transformation. In this study, we found that the Src homology (SH) 3 domain of Cas blocked v-Src-stimulated anchorage-independent cell growth, Matrigel invasion, and tumor growth in nude mice. Biochemical analysis revealed that the Cas SH3 domain selectively inhibited v-Src-stimulated activations of AKT and JNK, but not ERK and STAT3. Attenuation of the AKT pathway by the Cas SH3 domain rendered v-Src-transformed cells susceptible to apoptosis. Inhibition of the JNK pathway by the Cas SH3 domain led to suppression of v-Src-stimulated invasion. Taken together, our results indicate that the Cas SH3 domain has an anti-tumor function, which severely impairs the transforming potential of v-Src.

【 授权许可】

Unknown