Targeting MCT-1 oncogene inhibits Shc pathway and xenograft tumorigenicity

// Hung-Ju Shih 1,2 , Hsiao-Huei Chen 1 , Yen-An Chen 1 , Meng-Hsun Wu 1 , Gan-Guang Liou 1 , Wei-Wen Chang 2 , Linyi Chen 3 , Lu-Hai Wang 1 , Hsin-Ling Hsu 1 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.