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

Chi Hung Cheng; Kuo Ching Yu; Hsin Ling Chen; Shu Yi Chen; Chi Hui Huang; Po Chao Chan; Chiung Wha Wung; Hong Chen Chen

doi:10.1016/S0014-5793(03)01501-1

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

Chi Hung Cheng, Kuo Ching Yu, Hsin Ling Chen, Shu Yi Chen, Chi Hui Huang, Po Chao Chan, Chiung Wha Wung, Hong Chen Chen^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	221-227
Number of pages	7
Journal	FEBS Letters
Volume	557
Issue number	1-3
DOIs	https://doi.org/10.1016/S0014-5793(03)01501-1
State	Published - 16 Jan 2004

Keywords

Anoikis
Crk-associated substrate
Invasion
Src
Src homology 3 domain
Tumor

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10.1016/S0014-5793(03)01501-1

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@article{50e8d8e9fe6d426cbba37a57fd76526e,

title = "Blockade of v-Src-stimulated tumor formation by the Src homology 3 domain of Crk-associated substrate (Cas)",

abstract = "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.",

keywords = "Anoikis, Crk-associated substrate, Invasion, Src, Src homology 3 domain, Tumor",

author = "Cheng, {Chi Hung} and Yu, {Kuo Ching} and Chen, {Hsin Ling} and Chen, {Shu Yi} and Huang, {Chi Hui} and Chan, {Po Chao} and Wung, {Chiung Wha} and Chen, {Hong Chen}",

note = "Funding Information: This work was supported by the National Science Council, Taiwan (Grants NSC-92-2311-B-005-035 and NSC-92-2320-B-005-007), Taichung Veterans General Hospital, and National Chung Hsing University (Grants 91VH-13 and TCVGH-NCHU-927613).",

year = "2004",

month = jan,

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doi = "10.1016/S0014-5793(03)01501-1",

language = "English",

volume = "557",

pages = "221--227",

journal = "FEBS Letters",

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T1 - Blockade of v-Src-stimulated tumor formation by the Src homology 3 domain of Crk-associated substrate (Cas)

AU - Cheng, Chi Hung

AU - Yu, Kuo Ching

AU - Chen, Hsin Ling

AU - Chen, Shu Yi

AU - Huang, Chi Hui

AU - Chan, Po Chao

AU - Wung, Chiung Wha

AU - Chen, Hong Chen

N1 - Funding Information: This work was supported by the National Science Council, Taiwan (Grants NSC-92-2311-B-005-035 and NSC-92-2320-B-005-007), Taichung Veterans General Hospital, and National Chung Hsing University (Grants 91VH-13 and TCVGH-NCHU-927613).

PY - 2004/1/16

Y1 - 2004/1/16

N2 - 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.

AB - 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.

KW - Anoikis

KW - Crk-associated substrate

KW - Invasion

KW - Src

KW - Src homology 3 domain

KW - Tumor

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AN - SCOPUS:1642491744

SN - 0014-5793

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JO - FEBS Letters

JF - FEBS Letters

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ER -

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

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