TMED3 exerts a protumor function in non-small cell lung cancer by enhancing the Wnt/β-catenin pathway via regulation of AKT

Transmembrane emp24 protein transport domain containing 3 (TMED3) is a newly identified cancer-related protein in several malignancies. However, its role in carcinogenesis is still controversial. The project was performed to explore the possible function of TMED3 in the carcinogenesis of non-small cell lung cancer (NSCLC). TMED3 were abundantly expressed in NSCLC tissue, and high TMED3 levels predicted reduced survival in NSCLC patients. NSCLC cells with TMED3 silencing proliferated and invaded more slowly, and were more sensitive to the chemotherapy drug cisplatin than control NSCLC cells. TMED3 silencing reduced the activity of Wnt/beta-catenin pathway, associated with the repression of AKT. Restraint of AKT blocked TMED3-overexpressionevoked enhancing effects on Wnt/beta-catenin pathway. Moreover, down-regulating Wnt/beta-catenin activity reversed TMED3-overexpression-evoked enhancing effects on the proliferation and invasion of NSCLC cells. Additionally, inhibition of TMED3 also displayed antitumor effects in vivo in nude mice. Taken together, our data demonstrate that TMED3 exerts a protumor function in NSCLC by enhancing Wnt/beta-catenin signaling by modulating AKT. Our findings demonstrate that TMED3 inhibition displayed outstanding antitumor effects in vitro and in vivo, and may be a candidate target for future exploiting targeted therapies for NSCLC management.