期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 11, 页码 -出版社
MDPI
DOI: 10.3390/ijms22115543
关键词
liver; HCC; EMT; TGF-beta; lipid metabolism; oxidative metabolism; beta oxidation
资金
- People Programme (Marie Curie Actions) of the FP72013 under REA grant agreement [PITN-GA-2012-316549]
- Agencia Estatal de Investigacion, Ministry of Science and Innovation, Spain
- FEDER funds/European Regional Development Fund-a way to build Europe
- FPI program [SAF2015-64149-R, RTI2018-094079, FPI -BES-2016-077564, PID2019106209RB-I00, RED2018-102576-T]
- Instituto de Salud Carlos III, Spain
EMT induced by TGF-beta in HCC cells reprograms lipid metabolism to facilitate the utilization of FFA and the entry of acetyl-CoA into the TCA cycle, to sustain the elevated requirements of energy linked to this process.
(1) Background: The transforming growth factor (TGF)-beta plays a dual role in liver carcinogenesis. At early stages, it inhibits cell growth and induces apoptosis. However, TGF-beta expression is high in advanced stages of hepatocellular carcinoma (HCC) and cells become resistant to TGF-beta induced suppressor effects, responding to this cytokine undergoing epithelial-mesenchymal transition (EMT), which contributes to cell migration and invasion. Metabolic reprogramming has been established as a key hallmark of cancer. However, to consider metabolism as a therapeutic target in HCC, it is necessary to obtain a better understanding of how reprogramming occurs, which are the factors that regulate it, and how to identify the situation in a patient. Accordingly, in this work we aimed to analyze whether a process of full EMT induced by TGF-beta in HCC cells induces metabolic reprogramming. (2) Methods: In vitro analysis in HCC cell lines, metabolomics and transcriptomics. (3) Results: Our findings indicate a differential metabolic switch in response to TGF-beta when the HCC cells undergo a full EMT, which would favor lipolysis, increased transport and utilization of free fatty acids (FFA), decreased aerobic glycolysis and an increase in mitochondrial oxidative metabolism. (4) Conclusions: EMT induced by TGF-beta in HCC cells reprograms lipid metabolism to facilitate the utilization of FFA and the entry of acetyl-CoA into the TCA cycle, to sustain the elevated requirements of energy linked to this process.
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