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LKB1/STK11 Tumor Suppressor Reduces Angiogenesis by Directly Interacting with VEGFR2 in Tumorigenesis

Seung Bae Rho1, Hyun Jung Byun2, Boh-Ram Kim2

  • 1Division of Cancer Biology, Research Institute, National Cancer Center, Goyang 10408, Republic of Korea.

Biomolecules & Therapeutics
|June 25, 2023
PubMed

Insights

The liver kinase B1 (LKB1) tumor suppressor inhibits cervical cancer growth by blocking new blood vessel formation. LKB1 reduces tumor angiogenesis by targeting key molecular pathways, offering potential new therapeutic strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Cervical cancer is a common malignancy in women, with current treatments including surgery, radiotherapy, and chemotherapy.
  • Tumor angiogenesis, the formation of new blood vessels, is critical for cervical tumor progression.
  • The precise molecular mechanisms by which the liver kinase B1 (LKB1/STK11) tumor suppressor influences cervical tumor angiogenesis remain unclear.

Purpose of the Study:

  • To elucidate the role of LKB1 in regulating cervical tumor angiogenesis.
  • To investigate the molecular mechanisms through which LKB1 exerts its anti-angiogenic effects in cervical cancer.

Main Methods:

  • In vitro and in vivo experimental models of cervical cancer.
  • Assessment of LKB1 expression and its impact on angiogenesis-related factors.
  • Analysis of LKB1 interaction with VEGF receptor 2 (VEGFR-2) and downstream signaling pathways.

Main Results:

  • LKB1 significantly inhibited cervical tumor angiogenesis by suppressing vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1α expression.
  • LKB1 demonstrated direct inhibitory effects on both carcinoma and vascular endothelial cells, leading to reduced tumor growth.
  • LKB1 was identified to bind VEGFR-2, modulating the VEGFR-2-mediated protein kinase B/mechanistic target of rapamycin signaling pathway in endothelial cells.

Conclusions:

  • LKB1 possesses potent anti-angiogenic and anti-tumor properties in cervical cancer.
  • The findings reveal LKB1's mechanism of action involves suppressing VEGF and targeting the VEGFR-2/Akt/mTOR pathway.
  • This study provides a foundation for developing novel LKB1-based therapeutic strategies for cervical cancer.
Keywords:
Anti-angiogenic activityCell cycleHypoxic environment conditionsLKB1/STK11 tumor suppressorProtein-protein interaction

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