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Blockade of v‐Src‐stimulated tumor formation by the Src homology 3 domain of Crk‐associated substrate (Cas)
Author(s) -
Cheng Chi-Hung,
Yu Kuo-Ching,
Chen Hsin-Ling,
Chen Shu-Yi,
Huang Chi-Hui,
Chan Po-Chao,
Wung Chiung-Wha,
Chen Hong-Chen
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)01501-1
Subject(s) - proto oncogene tyrosine protein kinase src , sh3 domain , protein kinase b , adapter molecule crk , chemistry , sh2 domain , microbiology and biotechnology , cancer research , signal transduction , biology , signal transducing adaptor protein
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.