Roles of THG-1 on cellular proliferation, differentiation and tumorgenesis

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THG-1/Tsc22D4 belongs to Tsc-22 family members. However, biological and physiological roles of THG-1 remain unclear. We found that THG-1 is localized in basal layer of normal squamous epithelium, and overexpressed in squamous cell carcinomas. Knockdown of THG-1 in tumor cells suppresses cell proliferation, invasiveness and tumorigenicity. Moreover, overexpression of THG-1 suppresses the differentiation in squamous epithelium formation. We also found that THG-1 is phosphorylated by Ras-ERK pathway, which is required for the promotion of cellular proliferation by EGF and Ras-mediated tumorigenesis. Furthermore, we found an oncogenic mutation of THG-1 in tumors. These findings highlight the importance of THG-1 as a novel oncogene of squamous cell carcinomas.