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Oncotarget. 2012 Nov;3(11):1401-15.

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

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1
Institute of Molecular and Genomic Medicine, National Health Research Institutes, Taiwan.

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.

PMID:
23211466
PMCID:
PMC3717801
DOI:
10.18632/oncotarget.688
[Indexed for MEDLINE]
Free PMC Article
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