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Shifting the Gears of Metabolic Plasticity to Drive Cell State Transitions in Cancer

SIMPLE SUMMARY: Metabolic adaptation by cancer cells is enabled through the rewiring of metabolic processes, thereby allowing them to survive and thrive in diverse tissue microenvironments. It is also exploited to maintain cancer stemness, drive epithelial–mesenchymal transition, and gain therapy re...

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Autores principales: Wu, Zhengwei, Lee, Yi Fei, Yeo, Xun Hui, Loo, Ser Yue, Tam, Wai Leong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999312/
https://www.ncbi.nlm.nih.gov/pubmed/33804114
http://dx.doi.org/10.3390/cancers13061316
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author Wu, Zhengwei
Lee, Yi Fei
Yeo, Xun Hui
Loo, Ser Yue
Tam, Wai Leong
author_facet Wu, Zhengwei
Lee, Yi Fei
Yeo, Xun Hui
Loo, Ser Yue
Tam, Wai Leong
author_sort Wu, Zhengwei
collection PubMed
description SIMPLE SUMMARY: Metabolic adaptation by cancer cells is enabled through the rewiring of metabolic processes, thereby allowing them to survive and thrive in diverse tissue microenvironments. It is also exploited to maintain cancer stemness, drive epithelial–mesenchymal transition, and gain therapy resistance. These critical cellular events are pertinent to the various steps of cancer progression. Mechanistic insights into nutrient addiction arising from such metabolic rewiring have revealed therapeutic vulnerabilities that can be exploited as novel treatment modalities or for drug development. This review discusses concepts and principles of metabolic plasticity and highlights current preclinical and clinical strategies aimed at targeting these metabolic derangements. ABSTRACT: Cancer metabolism is a hallmark of cancer. Metabolic plasticity defines the ability of cancer cells to reprogram a plethora of metabolic pathways to meet unique energetic needs during the various steps of disease progression. Cell state transitions are phenotypic adaptations which confer distinct advantages that help cancer cells overcome progression hurdles, that include tumor initiation, expansive growth, resistance to therapy, metastasis, colonization, and relapse. It is increasingly appreciated that cancer cells need to appropriately reprogram their cellular metabolism in a timely manner to support the changes associated with new phenotypic cell states. We discuss metabolic alterations that may be adopted by cancer cells in relation to the maintenance of cancer stemness, activation of the epithelial–mesenchymal transition program for facilitating metastasis, and the acquisition of drug resistance. While such metabolic plasticity is harnessed by cancer cells for survival, their dependence and addiction towards certain metabolic pathways also present therapeutic opportunities that may be exploited.
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spelling pubmed-79993122021-03-28 Shifting the Gears of Metabolic Plasticity to Drive Cell State Transitions in Cancer Wu, Zhengwei Lee, Yi Fei Yeo, Xun Hui Loo, Ser Yue Tam, Wai Leong Cancers (Basel) Review SIMPLE SUMMARY: Metabolic adaptation by cancer cells is enabled through the rewiring of metabolic processes, thereby allowing them to survive and thrive in diverse tissue microenvironments. It is also exploited to maintain cancer stemness, drive epithelial–mesenchymal transition, and gain therapy resistance. These critical cellular events are pertinent to the various steps of cancer progression. Mechanistic insights into nutrient addiction arising from such metabolic rewiring have revealed therapeutic vulnerabilities that can be exploited as novel treatment modalities or for drug development. This review discusses concepts and principles of metabolic plasticity and highlights current preclinical and clinical strategies aimed at targeting these metabolic derangements. ABSTRACT: Cancer metabolism is a hallmark of cancer. Metabolic plasticity defines the ability of cancer cells to reprogram a plethora of metabolic pathways to meet unique energetic needs during the various steps of disease progression. Cell state transitions are phenotypic adaptations which confer distinct advantages that help cancer cells overcome progression hurdles, that include tumor initiation, expansive growth, resistance to therapy, metastasis, colonization, and relapse. It is increasingly appreciated that cancer cells need to appropriately reprogram their cellular metabolism in a timely manner to support the changes associated with new phenotypic cell states. We discuss metabolic alterations that may be adopted by cancer cells in relation to the maintenance of cancer stemness, activation of the epithelial–mesenchymal transition program for facilitating metastasis, and the acquisition of drug resistance. While such metabolic plasticity is harnessed by cancer cells for survival, their dependence and addiction towards certain metabolic pathways also present therapeutic opportunities that may be exploited. MDPI 2021-03-15 /pmc/articles/PMC7999312/ /pubmed/33804114 http://dx.doi.org/10.3390/cancers13061316 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Wu, Zhengwei
Lee, Yi Fei
Yeo, Xun Hui
Loo, Ser Yue
Tam, Wai Leong
Shifting the Gears of Metabolic Plasticity to Drive Cell State Transitions in Cancer
title Shifting the Gears of Metabolic Plasticity to Drive Cell State Transitions in Cancer
title_full Shifting the Gears of Metabolic Plasticity to Drive Cell State Transitions in Cancer
title_fullStr Shifting the Gears of Metabolic Plasticity to Drive Cell State Transitions in Cancer
title_full_unstemmed Shifting the Gears of Metabolic Plasticity to Drive Cell State Transitions in Cancer
title_short Shifting the Gears of Metabolic Plasticity to Drive Cell State Transitions in Cancer
title_sort shifting the gears of metabolic plasticity to drive cell state transitions in cancer
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999312/
https://www.ncbi.nlm.nih.gov/pubmed/33804114
http://dx.doi.org/10.3390/cancers13061316
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