Translationally Controlled Tumor Protein Enhances Angiogenesis in Ovarian Tumors by Activating Vascular Endothelial Growth Factor Receptor 2 Signaling

Abstract

Translationally controlled tumor protein (TCTP) is a regulatory protein that plays pivotal roles in cellular processes including the cell cycle, apoptosis, microtubule stabilization, embryo development, stress responses, and cancer. However, the molecular mechanism by which it promotes tumor angiogenesis is still unclear. In this study, we explored the mechanisms underlying stimulation of angiogenesis by a novel TCTP. Recombinant TCTP enhanced vascular endothelial growth factor (VEGF)-induced endothelial cell migration, capillary-like tubular structure formation, and cell proliferation by interacting with VEGF receptor 2 (VEGFR-2) in vitro. In contrast, we showed that TCTP knockdown (using short interfering [si]TCTP) led to a decrease in ovarian tumor cells. We also examined the expression of VEGF and hypoxia inducible factor 1 (HIF-1 alpha), an important angiogenic factor. The expression of VEGF as well as HIF-1 alpha was dramatically decreased by siTCTP. Mechanistically, siTCTP inhibited VEGFR-2 tyrosine phosphorylation and phosphorylation of its downstream targets PI3K, Akt, and mTOR. Collectively, these findings indicate that TCTP can promote proliferation and angiogenesis via the VEGFR-2/PI3K and mTOR signaling pathways in ovarian tumor cells, providing new insight into the mechanism behind the involvement of TCTP in tumor angiogenesis.