2026-04-13T07:20:48Zhttps://recercat.cat/oai/requestoai:recercat.cat:2445/1259702025-12-04T21:13:20Zcom_2072_1057col_2072_478781col_2072_478799col_2072_478916col_2072_478908col_2072_478917
RECERCAT
author
Soukupova, Jitka
author
Malfettone, Andrea
author
Hyroššová, Petra
author
Hernández-Alvarez, María Isabel
author
Peñuelas Haro, Irene
author
Bertran Rodríguez, Esther
author
Junza Martínez, Alexandra
author
Capellades, Jordi
author
Giannelli, Gianluigi
author
Yanes, Oscar
author
Zorzano Olarte, Antonio
author
Perales Losa, Carlos
author
Fabregat Romero, Isabel
2018-11-09T15:25:24Z2018-11-09T15:25:24Z2017-10-022018-11-09T15:25:25Z
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.
cc-by (c) Soukupova, J. et al., 2017 http://creativecommons.org/licenses/by/3.0/es info:eu-repo/semantics/openAccess
Mutació (Biologia)
Càncer
Mutation (Biology)
Cancer
Role of the Transforming Growth Factor-β in regulating hepatocellular carcinoma oxidative metabolism.
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion