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Targeting MCT-1 oncogene inhibits Shc pathway and xenograft tumorigenicity.

ABSTRACT: Overexpression of Shc adaptor proteins is associated with mitogenesis, carcinogenesis and metastasis. Multiple copies in T-cell malignancy 1 (MCT-1) oncoprotein promotes cell proliferation, survival and tumorigenic effects. Our current data show that MCT-1 is a novel regulator of Shc-Ras-MEK-ERK signaling and MCT-1 is significantly co-activated with Shc gene in human carcinomas. The knockdown of MCT-1 enhances apoptotic cell death accompanied with the activation of caspases and cleavage of caspase substrates under environmental stress. The cancer cell proliferation, chemo-resistance and tumorigenic capacity are proved to be effectively suppressed by targeting MCT-1. Accordingly, an important linkage between MCT-1 oncogenicity and Shc pathway in tumor development has now been established. Promoting MCT-1 expression by gene hyperactivation may be recognized as a tumor marker and MCT-1 may serve as a molecular target of cancer therapy.

SUBMITTER: Shih HJ

PROVIDER: S-EPMC3717801 | biostudies-other | 2012 Nov

REPOSITORIES: biostudies-other

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Targeting MCT-1 oncogene inhibits Shc pathway and xenograft tumorigenicity.

Shih Hung-Ju HJ Chen Hsiao-Huei HH Chen Yen-An YA Wu Meng-Hsun MH Liou Gan-Guang GG Chang Wei-Wen WW Chen Linyi L Wang Lu-Hai LH Hsu Hsin-Ling HL

Oncotarget 20121101 11

Overexpression of Shc adaptor proteins is associated with mitogenesis, carcinogenesis and metastasis. Multiple copies in T-cell malignancy 1 (MCT-1) oncoprotein promotes cell proliferation, survival and tumorigenic effects. Our current data show that MCT-1 is a novel regulator of Shc-Ras-MEK-ERK signaling and MCT-1 is significantly co-activated with Shc gene in human carcinomas. The knockdown of MCT-1 enhances apoptotic cell death accompanied with the activation of caspases and cleavage of caspa ...[more]

PMID: 23211466

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