Downregulated Trophinin-Associated Protein Plays a Critical Role in Human Hepatocellular Carcinoma Through Upregulation of Tumor Cell Growth and Migration.

ABSTRACT

Trophinin-associated protein (TROAP) was a protein first identified to mediate the process of embryo transplantation and later found to be involved in microtubule regulation. However, little is known about the role of TROAP in hepatocellular carcinoma (HCC). In the present study, we reported that both TROAP mRNA and protein expressions were downregulated in human HCC samples as well as cell lines. A high level of TROAP was associated with small tumor size (p < 0.05), minor tumor nodules (p < 0.01), and mild vein invasion (p < 0.05). We further constructed in vitro TROAP depletion and overexpression HCC cell models. TROAP depletion significantly enhanced the proliferation and colony formation abilities, whereas TROAP overexpression had an inhibitory effect on the growth of HCC cells. The G1/S phase arrest by TROAP overexpression correlated with increased cell cycle inhibitors p21 and p27, and declined cell cycle promoting kinase complex CDK6/cyclin D1. Depressed TROAP expression enhanced the migration ability, while the opposite influence was observed in TROAP-overexpressed HCC cells. Taken together, these results indicate that TROAP suppresses cellular growth and migration in HCC. This discovery will further our understanding of the pathogenic mechanisms of human HCC.