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Hypoxia-Inducible Factor 2-Dependent Pathways Driving Von Hippel–Lindau-Deficient Renal Cancer

The most common type of the renal cancers detected in humans is clear cell renal cell carcinomas (ccRCCs). These tumors are usually initiated by biallelic gene inactivation of the Von Hippel–Lindau (VHL) factor in the renal epithelium, which deregulates the hypoxia-inducible factors (HIFs) HIF1α and...

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Autores principales: Meléndez-Rodríguez, Florinda, Roche, Olga, Sanchez-Prieto, Ricardo, Aragones, Julian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6002531/
https://www.ncbi.nlm.nih.gov/pubmed/29938199
http://dx.doi.org/10.3389/fonc.2018.00214
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author Meléndez-Rodríguez, Florinda
Roche, Olga
Sanchez-Prieto, Ricardo
Aragones, Julian
author_facet Meléndez-Rodríguez, Florinda
Roche, Olga
Sanchez-Prieto, Ricardo
Aragones, Julian
author_sort Meléndez-Rodríguez, Florinda
collection PubMed
description The most common type of the renal cancers detected in humans is clear cell renal cell carcinomas (ccRCCs). These tumors are usually initiated by biallelic gene inactivation of the Von Hippel–Lindau (VHL) factor in the renal epithelium, which deregulates the hypoxia-inducible factors (HIFs) HIF1α and HIF2α, and provokes their constitutive activation irrespective of the cellular oxygen availability. While HIF1α can act as a ccRCC tumor suppressor, HIF2α has emerged as the key HIF isoform that is essential for ccRCC tumor progression. Indeed, preclinical and clinical data have shown that pharmacological inhibitors of HIF2α can efficiently combat ccRCC growth. In this review, we discuss the molecular basis underlying the oncogenic potential of HIF2α in ccRCC by focusing on those pathways primarily controlled by HIF2α that are thought to influence the progression of these tumors.
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spelling pubmed-60025312018-06-22 Hypoxia-Inducible Factor 2-Dependent Pathways Driving Von Hippel–Lindau-Deficient Renal Cancer Meléndez-Rodríguez, Florinda Roche, Olga Sanchez-Prieto, Ricardo Aragones, Julian Front Oncol Oncology The most common type of the renal cancers detected in humans is clear cell renal cell carcinomas (ccRCCs). These tumors are usually initiated by biallelic gene inactivation of the Von Hippel–Lindau (VHL) factor in the renal epithelium, which deregulates the hypoxia-inducible factors (HIFs) HIF1α and HIF2α, and provokes their constitutive activation irrespective of the cellular oxygen availability. While HIF1α can act as a ccRCC tumor suppressor, HIF2α has emerged as the key HIF isoform that is essential for ccRCC tumor progression. Indeed, preclinical and clinical data have shown that pharmacological inhibitors of HIF2α can efficiently combat ccRCC growth. In this review, we discuss the molecular basis underlying the oncogenic potential of HIF2α in ccRCC by focusing on those pathways primarily controlled by HIF2α that are thought to influence the progression of these tumors. Frontiers Media S.A. 2018-06-08 /pmc/articles/PMC6002531/ /pubmed/29938199 http://dx.doi.org/10.3389/fonc.2018.00214 Text en Copyright © 2018 Meléndez-Rodríguez, Roche, Sanchez-Prieto and Aragones. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Meléndez-Rodríguez, Florinda
Roche, Olga
Sanchez-Prieto, Ricardo
Aragones, Julian
Hypoxia-Inducible Factor 2-Dependent Pathways Driving Von Hippel–Lindau-Deficient Renal Cancer
title Hypoxia-Inducible Factor 2-Dependent Pathways Driving Von Hippel–Lindau-Deficient Renal Cancer
title_full Hypoxia-Inducible Factor 2-Dependent Pathways Driving Von Hippel–Lindau-Deficient Renal Cancer
title_fullStr Hypoxia-Inducible Factor 2-Dependent Pathways Driving Von Hippel–Lindau-Deficient Renal Cancer
title_full_unstemmed Hypoxia-Inducible Factor 2-Dependent Pathways Driving Von Hippel–Lindau-Deficient Renal Cancer
title_short Hypoxia-Inducible Factor 2-Dependent Pathways Driving Von Hippel–Lindau-Deficient Renal Cancer
title_sort hypoxia-inducible factor 2-dependent pathways driving von hippel–lindau-deficient renal cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6002531/
https://www.ncbi.nlm.nih.gov/pubmed/29938199
http://dx.doi.org/10.3389/fonc.2018.00214
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