Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Translationally Controlled Tumor Protein Enhances Angiogenesis in Ovarian Tumors by Activating Vascular Endothelial Growth Factor Receptor 2 Signaling

  • Seung Bae Rho (Division of Cancer Biology, Research Institute, National Cancer Center) ;
  • Boh-Ram Kim (College of Pharmacy, Dongguk University) ;
  • Seung-Hoon Lee (Department of Life Science, Yong In University) ;
  • Chang Hoon Lee (College of Pharmacy, Dongguk University)
  • Received : 2024.10.30
  • Accepted : 2024.11.25
  • Published : 2025.01.01
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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-1α), an important angiogenic factor. The expression of VEGF as well as HIF-1α 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.

Keywords

Acknowledgement

This work was supported by a grant from the National Cancer Center, Korea (NCC-2210450-2 and 2310590-1) and the Basic Science Research Program through the NRF (NRF-2020R1A2C3004973, NRF-2018R1A5A2023127).

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