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2017-10-02

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cc-by (c) Soukupova, J. et al., 2017
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/125970

Role of the Transforming Growth Factor-β in regulating hepatocellular carcinoma oxidative metabolism.

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https://doi.org/10.1038/s41598-017-12837-y

Abstract

Transforming Growth Factor beta (TGF-β) induces tumor cell migration and invasion. However, its role in inducing metabolic reprogramming is poorly understood. Here we analyzed the metabolic profle of hepatocellular carcinoma (HCC) cells that show diferences in TGF-β expression. Oxygen consumption rate (OCR), extracellular acidifcation rate (ECAR), metabolomics and transcriptomics were performed. Results indicated that the switch from an epithelial to a mesenchymal/migratory phenotype in HCC cells is characterized by reduced mitochondrial respiration, without signifcant diferences in glycolytic activity. Concomitantly, enhanced glutamine anaplerosis and biosynthetic use of TCA metabolites were proved through analysis of metabolite levels, as well as metabolic fuxes from U-13C6-Glucose and U-13C5-Glutamine. This correlated with increase in glutaminase 1 (GLS1) expression, whose inhibition reduced cell migration. Experiments where TGF-β function was activated with extracellular TGF-β1 or inhibited through TGF-β receptor I silencing showed that TGF-β induces a switch from oxidative metabolism, coincident with a decrease in OCR and the upregulation of glutamine transporter Solute Carrier Family 7 Member 5 (SLC7A5) and GLS1. TGF-β also regulated the expression of key genes involved in the fux of glycolytic intermediates and fatty acid metabolism. Together, these results indicate that autocrine activation of the TGF-β pathway regulates oxidative metabolism in HCC cells.

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Mutació (Biologia), Càncer

Subject (English)

Mutation (Biology), Cancer

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Articles publicats en revistes (Ciències Fisiològiques)
Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))
Publicacions de projectes de recerca finançats per la UE

Citation

SOUKUPOVA, Jitka, et al. Role of the Transforming Growth Factor-β in regulating hepatocellular carcinoma oxidative metabolism. Scientific Reports. 2017. Vol. 7, num. 12486. ISSN 2045-2322. [consulted: 18 of August of 2026]. Available at: https://hdl.handle.net/2445/125970

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