Targeting MCT-1 oncogene inhibits Shc pathway and xenograft tumorigenicity

Hung-Ju Shih; Hsiao-Huei Chen; Yen-An Chen; Meng-Hsun Wu; Gan-Guang Liou; Wei-Wen Chang; Linyi Chen; Lu-Hai Wang; Hsin-Ling Hsu

doi:10.18632/oncotarget.688

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Research Papers:

Targeting MCT-1 oncogene inhibits Shc pathway and xenograft tumorigenicity

Hung-Ju Shih, Hsiao-Huei Chen, Yen-An Chen, Meng-Hsun Wu, Gan-Guang Liou, Wei-Wen Chang, Linyi Chen, Lu-Hai Wang and Hsin-Ling Hsu _

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Oncotarget. 2012; 3:1401-1415. https://doi.org/10.18632/oncotarget.688

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Abstract

Hung-Ju Shih1,2, Hsiao-Huei Chen1, Yen-An Chen1, Meng-Hsun Wu1, Gan-Guang Liou1, Wei-Wen Chang2, Linyi Chen3, Lu-Hai Wang1, Hsin-Ling Hsu1

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

2 Division of General Surgery, Wan Fang Hospital, Taipei Medical University, Taiwan

3 Institute of Molecular Medicine and Department of Medical Science, National Tsing Hua University, Taiwan

Correspondence:

Hsin-Ling Hsu, email:

Keywords: MCT-1, Shc, Ras, ERK, apoptosis, tumor

Received: October 01, 2012, Accepted: November 06, 2012, Published: November 09, 2012

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.

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Research Papers:

Targeting MCT-1 oncogene inhibits Shc pathway and xenograft tumorigenicity

Abstract