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

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 ef...

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Autores principales: Rho, Seung Bae, Byun, Hyun Jung, Kim, Boh-Ram, Lee, Chang Hoon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Society of Applied Pharmacology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10315345/
https://www.ncbi.nlm.nih.gov/pubmed/37357018
http://dx.doi.org/10.4062/biomolther.2023.106
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author Rho, Seung Bae
Byun, Hyun Jung
Kim, Boh-Ram
Lee, Chang Hoon
author_facet Rho, Seung Bae
Byun, Hyun Jung
Kim, Boh-Ram
Lee, Chang Hoon
author_sort Rho, Seung Bae
collection PubMed
description 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.
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spelling pubmed-103153452023-07-04 LKB1/STK11 Tumor Suppressor Reduces Angiogenesis by Directly Interacting with VEGFR2 in Tumorigenesis Rho, Seung Bae Byun, Hyun Jung Kim, Boh-Ram Lee, Chang Hoon Biomol Ther (Seoul) Original Article 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. The Korean Society of Applied Pharmacology 2023-07-01 2023-06-26 /pmc/articles/PMC10315345/ /pubmed/37357018 http://dx.doi.org/10.4062/biomolther.2023.106 Text en Copyright © 2023, The Korean Society of Applied Pharmacology https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0 (https://creativecommons.org/licenses/by-nc/4.0/) ) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Rho, Seung Bae
Byun, Hyun Jung
Kim, Boh-Ram
Lee, Chang Hoon
LKB1/STK11 Tumor Suppressor Reduces Angiogenesis by Directly Interacting with VEGFR2 in Tumorigenesis
title LKB1/STK11 Tumor Suppressor Reduces Angiogenesis by Directly Interacting with VEGFR2 in Tumorigenesis
title_full LKB1/STK11 Tumor Suppressor Reduces Angiogenesis by Directly Interacting with VEGFR2 in Tumorigenesis
title_fullStr LKB1/STK11 Tumor Suppressor Reduces Angiogenesis by Directly Interacting with VEGFR2 in Tumorigenesis
title_full_unstemmed LKB1/STK11 Tumor Suppressor Reduces Angiogenesis by Directly Interacting with VEGFR2 in Tumorigenesis
title_short LKB1/STK11 Tumor Suppressor Reduces Angiogenesis by Directly Interacting with VEGFR2 in Tumorigenesis
title_sort lkb1/stk11 tumor suppressor reduces angiogenesis by directly interacting with vegfr2 in tumorigenesis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10315345/
https://www.ncbi.nlm.nih.gov/pubmed/37357018
http://dx.doi.org/10.4062/biomolther.2023.106
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