TCRP1 promotes NIH/3T3 cell transformation by over-activating PDK1 and AKT1

Abstract

Tongue cancer resistance-related protein 1 (TCRP1) gene was first cloned from the multidrug resistance tongue cancer cell (Tca8113/pingyangmycin) in our lab. Our precious studies demonstrated that TCRP1 was involving in chemotherapy and radiotherapy resistance of tongue cancer cells, lung cancer cells and ovarian cancer cells. In this study, we showed that TCRP1 overexpression promotes cell transformation and tumorigenesis through hyperphosphorylation of the oncogenic kinase 3-phosphoinositide-dependent protein kinase-1 (PDK1) and AKT1, whereas inhibition of PDK1 by OSU-03012 or PDK1 small interfering RNA reversed TCRP1-mediated cell transformation. Importantly, TCRP1 was able to directly interact with PDK1, and 93-107 amino-acid and 109-124 amino-acid sites of TCRP1 were the common binding domain of PDK1. Moreover, in line with its oncogenic activity, we found that TCRP1 is often overexpressed in human in lung cancer, glioma, ovarian cancer, thyroid cancer, nasopharyngeal carcinoma, pancreatic cancer, stomach cancer and tongue carcinoma tissues. Spearman correlation analysis showed that the expression of TCRP1 has a positive correlation with p-PDK1, as well as p-AKT1 in lung cancer and gliomas tissues. Thus, TCRP1 may be a candidate as human oncoprotein that promotes cancer development by activation of PDK1/AKT1 signaling.