TGFβ-induced metabolic reprogramming during epithelial-to-mesenchymal transition in cancer
Metastasis is the most frequent cause of death in cancer patients. Epithelial-to-mesenchymal transition (EMT) is the process in which cells lose epithelial integrity and become motile, a critical step for cancer cell invasion, drug resistance and immune evasion. The transforming growth factor-β (TGF...
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| Veröffentlicht in: | Cellular and molecular life sciences : CMLS 2020-06, Vol.77 (11), p.2103-2123 |
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| description | Metastasis is the most frequent cause of death in cancer patients. Epithelial-to-mesenchymal transition (EMT) is the process in which cells lose epithelial integrity and become motile, a critical step for cancer cell invasion, drug resistance and immune evasion. The transforming growth factor-β (TGFβ) signaling pathway is a major driver of EMT. Increasing evidence demonstrates that metabolic reprogramming is a hallmark of cancer and extensive metabolic changes are observed during EMT. The aim of this review is to summarize and interconnect recent findings that illustrate how changes in glycolysis, mitochondrial, lipid and choline metabolism coincide and functionally contribute to TGFβ-induced EMT. We describe TGFβ signaling is involved in stimulating both glycolysis and mitochondrial respiration. Interestingly, the subsequent metabolic consequences for the redox state and lipid metabolism in cancer cells are found to be in favor of EMT as well. Combined we illustrate that a better understanding of the mechanistic links between TGFβ signaling, cancer metabolism and EMT holds promising strategies for cancer therapy, some of which are already actively being explored in the clinic. |
| doi_str_mv | 10.1007/s00018-019-03398-6 |
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Epithelial-to-mesenchymal transition (EMT) is the process in which cells lose epithelial integrity and become motile, a critical step for cancer cell invasion, drug resistance and immune evasion. The transforming growth factor-β (TGFβ) signaling pathway is a major driver of EMT. Increasing evidence demonstrates that metabolic reprogramming is a hallmark of cancer and extensive metabolic changes are observed during EMT. The aim of this review is to summarize and interconnect recent findings that illustrate how changes in glycolysis, mitochondrial, lipid and choline metabolism coincide and functionally contribute to TGFβ-induced EMT. We describe TGFβ signaling is involved in stimulating both glycolysis and mitochondrial respiration. Interestingly, the subsequent metabolic consequences for the redox state and lipid metabolism in cancer cells are found to be in favor of EMT as well. Combined we illustrate that a better understanding of the mechanistic links between TGFβ signaling, cancer metabolism and EMT holds promising strategies for cancer therapy, some of which are already actively being explored in the clinic.</description><identifier>ISSN: 1420-682X</identifier><identifier>EISSN: 1420-9071</identifier><identifier>DOI: 10.1007/s00018-019-03398-6</identifier><identifier>PMID: 31822964</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Animals ; Biochemistry ; Biomedical and Life Sciences ; Biomedicine ; Cancer ; Cell Biology ; Cell Respiration ; Choline ; Drug resistance ; Epithelial-Mesenchymal Transition ; Glycolysis ; Growth factors ; Humans ; Life Sciences ; Lipid Metabolism ; Lipids ; Mesenchyme ; Metabolism ; Metastases ; Mitochondria ; Mitochondria - metabolism ; Mitochondria - pathology ; Neoplasms - metabolism ; Neoplasms - pathology ; Redox properties ; Review ; Signal Transduction ; Signaling ; Transforming Growth Factor beta - metabolism ; Transforming growth factor-b</subject><ispartof>Cellular and molecular life sciences : CMLS, 2020-06, Vol.77 (11), p.2103-2123</ispartof><rights>The Author(s) 2019</rights><rights>The Author(s) 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). 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Mol. Life Sci</addtitle><addtitle>Cell Mol Life Sci</addtitle><description>Metastasis is the most frequent cause of death in cancer patients. Epithelial-to-mesenchymal transition (EMT) is the process in which cells lose epithelial integrity and become motile, a critical step for cancer cell invasion, drug resistance and immune evasion. The transforming growth factor-β (TGFβ) signaling pathway is a major driver of EMT. Increasing evidence demonstrates that metabolic reprogramming is a hallmark of cancer and extensive metabolic changes are observed during EMT. The aim of this review is to summarize and interconnect recent findings that illustrate how changes in glycolysis, mitochondrial, lipid and choline metabolism coincide and functionally contribute to TGFβ-induced EMT. We describe TGFβ signaling is involved in stimulating both glycolysis and mitochondrial respiration. Interestingly, the subsequent metabolic consequences for the redox state and lipid metabolism in cancer cells are found to be in favor of EMT as well. 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Mol. Life Sci</stitle><addtitle>Cell Mol Life Sci</addtitle><date>2020-06-01</date><risdate>2020</risdate><volume>77</volume><issue>11</issue><spage>2103</spage><epage>2123</epage><pages>2103-2123</pages><issn>1420-682X</issn><eissn>1420-9071</eissn><abstract>Metastasis is the most frequent cause of death in cancer patients. Epithelial-to-mesenchymal transition (EMT) is the process in which cells lose epithelial integrity and become motile, a critical step for cancer cell invasion, drug resistance and immune evasion. The transforming growth factor-β (TGFβ) signaling pathway is a major driver of EMT. Increasing evidence demonstrates that metabolic reprogramming is a hallmark of cancer and extensive metabolic changes are observed during EMT. The aim of this review is to summarize and interconnect recent findings that illustrate how changes in glycolysis, mitochondrial, lipid and choline metabolism coincide and functionally contribute to TGFβ-induced EMT. We describe TGFβ signaling is involved in stimulating both glycolysis and mitochondrial respiration. Interestingly, the subsequent metabolic consequences for the redox state and lipid metabolism in cancer cells are found to be in favor of EMT as well. Combined we illustrate that a better understanding of the mechanistic links between TGFβ signaling, cancer metabolism and EMT holds promising strategies for cancer therapy, some of which are already actively being explored in the clinic.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><pmid>31822964</pmid><doi>10.1007/s00018-019-03398-6</doi><tpages>21</tpages><orcidid>https://orcid.org/0000-0002-7234-342X</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Biochemistry Biomedical and Life Sciences Biomedicine Cancer Cell Biology Cell Respiration Choline Drug resistance Epithelial-Mesenchymal Transition Glycolysis Growth factors Humans Life Sciences Lipid Metabolism Lipids Mesenchyme Metabolism Metastases Mitochondria Mitochondria - metabolism Mitochondria - pathology Neoplasms - metabolism Neoplasms - pathology Redox properties Review Signal Transduction Signaling Transforming Growth Factor beta - metabolism Transforming growth factor-b |
| title | TGFβ-induced metabolic reprogramming during epithelial-to-mesenchymal transition in cancer |
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