Biomolecules & Therapeutics

  • 제31권4호
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  • Pages.456-465
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  • 2023
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  • 1976-9148(pISSN)
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  • 2005-4483(eISSN)
한국응용약물학회 (The Korean Society of Applied Pharmacology)
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LKB1/STK11 Tumor Suppressor Reduces Angiogenesis by Directly Interacting with VEGFR2 in Tumorigenesis

  • Seung Bae Rho (Division of Cancer Biology, Research Institute, National Cancer Center) ;
  • Hyun Jung Byun (College of Pharmacy, Dongguk University) ;
  • Boh-Ram Kim (College of Pharmacy, Dongguk University) ;
  • Chang Hoon Lee (College of Pharmacy, Dongguk University)
  • 투고 : 2023.06.02
  • 심사 : 2023.06.13
  • 발행 : 2023.07.01
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초록

Cervical tumors represent a prevalent form of cancer affecting women worldwide; current treatment options involve surgery, radiotherapy, and chemotherapy. Angiogenesis, the process of new blood vessel formation, is a crucial factor in cervical tumor growth. The molecular mechanisms underlying the effects of the liver kinase B1 (LKB1/STK11) tumor suppressor protein on tumor angiogenesis have not been elucidated. Therefore, we investigated the role of LKB1 in cervical tumor angiogenesis both in vitro and in vivo in this study. Our results demonstrated that LKB1 inhibited cervical tumor angiogenesis by suppressing the expression of angiogenesis-related factors such as vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1α. LKB1 directly affected both carcinoma and vascular endothelial cells, resulting in a significant reduction in tumor growth and angiogenesis. Furthermore, LKB1 was found to bind to VEGF receptor 2 (VEGFR-2) and target the VEGFR-2-mediated protein kinase B/mechanistic target of rapamycin signaling pathway in endothelial cells, thereby reducing cervical tumor growth and angiogenesis. Our study provides new insights into the molecular mechanisms underlying the anti-tumor and anti-angiogenic effects of LKB1 in cervical cancer. These findings will help develop new therapeutic strategies for cervical cancer.

키워드

과제정보

This work was supported by a grant from the National Cancer Center, Korea (NCC-2112500-1 and 2210450-1) and the Basic Science Research Program and the BK21 FOUR program through the NRF (NRF-2018R1A5A2023127, and NRF-2020R1A2C3004973).

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