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TGF-βRII regulates glucose metabolism in oral cancer-associated fibroblasts via promoting PKM2 nuclear translocation

Cancer-associated fibroblasts (CAFs) are highly heterogeneous and differentiated stromal cells that promote tumor progression via remodeling of extracellular matrix, maintenance of stemness, angiogenesis, and modulation of tumor metabolism. Aerobic glycolysis is characterized by an increased uptake...

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Autores principales: Wu, Fanglong, Wang, Shimeng, Zeng, Qingxiang, Liu, Junjiang, Yang, Jin, Mu, Jingtian, Xu, Hongdang, Wu, Lanyan, Gao, Qinghong, He, Xin, Liu, Ying, Zhou, Hongmei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8748622/
https://www.ncbi.nlm.nih.gov/pubmed/35013150
http://dx.doi.org/10.1038/s41420-021-00804-6
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author Wu, Fanglong
Wang, Shimeng
Zeng, Qingxiang
Liu, Junjiang
Yang, Jin
Mu, Jingtian
Xu, Hongdang
Wu, Lanyan
Gao, Qinghong
He, Xin
Liu, Ying
Zhou, Hongmei
author_facet Wu, Fanglong
Wang, Shimeng
Zeng, Qingxiang
Liu, Junjiang
Yang, Jin
Mu, Jingtian
Xu, Hongdang
Wu, Lanyan
Gao, Qinghong
He, Xin
Liu, Ying
Zhou, Hongmei
author_sort Wu, Fanglong
collection PubMed
description Cancer-associated fibroblasts (CAFs) are highly heterogeneous and differentiated stromal cells that promote tumor progression via remodeling of extracellular matrix, maintenance of stemness, angiogenesis, and modulation of tumor metabolism. Aerobic glycolysis is characterized by an increased uptake of glucose for conversion into lactate under sufficient oxygen conditions, and this metabolic process occurs at the site of energy exchange between CAFs and cancer cells. As a hallmark of cancer, metabolic reprogramming of CAFs is defined as reverse Warburg effect (RWE), characterized by increased lactate, glutamine, and pyruvate, etc. derived from aerobic glycolysis. Given that the TGF-β signal cascade plays a critical role in RWE mainly through metabolic reprogramming related proteins including pyruvate kinase muscle isozyme 2 (PKM2), however, the role of nuclear PKM2 in modifying glycolysis remains largely unknown. In this study, using a series of in vitro and in vivo experiments, we provide evidence that TGF-βRII overexpression suppresses glucose metabolism in CAFs by attenuating PKM2 nuclear translocation, thereby inhibiting oral cancer tumor growth. This study highlights a novel pathway that explains the role of TGF-βRII in CAFs glucose metabolism and suggests that targeting TGF-βRII in CAFs might represent a therapeutic approach for oral cancer.
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spelling pubmed-87486222022-01-20 TGF-βRII regulates glucose metabolism in oral cancer-associated fibroblasts via promoting PKM2 nuclear translocation Wu, Fanglong Wang, Shimeng Zeng, Qingxiang Liu, Junjiang Yang, Jin Mu, Jingtian Xu, Hongdang Wu, Lanyan Gao, Qinghong He, Xin Liu, Ying Zhou, Hongmei Cell Death Discov Article Cancer-associated fibroblasts (CAFs) are highly heterogeneous and differentiated stromal cells that promote tumor progression via remodeling of extracellular matrix, maintenance of stemness, angiogenesis, and modulation of tumor metabolism. Aerobic glycolysis is characterized by an increased uptake of glucose for conversion into lactate under sufficient oxygen conditions, and this metabolic process occurs at the site of energy exchange between CAFs and cancer cells. As a hallmark of cancer, metabolic reprogramming of CAFs is defined as reverse Warburg effect (RWE), characterized by increased lactate, glutamine, and pyruvate, etc. derived from aerobic glycolysis. Given that the TGF-β signal cascade plays a critical role in RWE mainly through metabolic reprogramming related proteins including pyruvate kinase muscle isozyme 2 (PKM2), however, the role of nuclear PKM2 in modifying glycolysis remains largely unknown. In this study, using a series of in vitro and in vivo experiments, we provide evidence that TGF-βRII overexpression suppresses glucose metabolism in CAFs by attenuating PKM2 nuclear translocation, thereby inhibiting oral cancer tumor growth. This study highlights a novel pathway that explains the role of TGF-βRII in CAFs glucose metabolism and suggests that targeting TGF-βRII in CAFs might represent a therapeutic approach for oral cancer. Nature Publishing Group UK 2022-01-10 /pmc/articles/PMC8748622/ /pubmed/35013150 http://dx.doi.org/10.1038/s41420-021-00804-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Wu, Fanglong
Wang, Shimeng
Zeng, Qingxiang
Liu, Junjiang
Yang, Jin
Mu, Jingtian
Xu, Hongdang
Wu, Lanyan
Gao, Qinghong
He, Xin
Liu, Ying
Zhou, Hongmei
TGF-βRII regulates glucose metabolism in oral cancer-associated fibroblasts via promoting PKM2 nuclear translocation
title TGF-βRII regulates glucose metabolism in oral cancer-associated fibroblasts via promoting PKM2 nuclear translocation
title_full TGF-βRII regulates glucose metabolism in oral cancer-associated fibroblasts via promoting PKM2 nuclear translocation
title_fullStr TGF-βRII regulates glucose metabolism in oral cancer-associated fibroblasts via promoting PKM2 nuclear translocation
title_full_unstemmed TGF-βRII regulates glucose metabolism in oral cancer-associated fibroblasts via promoting PKM2 nuclear translocation
title_short TGF-βRII regulates glucose metabolism in oral cancer-associated fibroblasts via promoting PKM2 nuclear translocation
title_sort tgf-βrii regulates glucose metabolism in oral cancer-associated fibroblasts via promoting pkm2 nuclear translocation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8748622/
https://www.ncbi.nlm.nih.gov/pubmed/35013150
http://dx.doi.org/10.1038/s41420-021-00804-6
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