TGFβ2-induced formation of lipid droplets supports acidosis-driven EMT and the metastatic spreading of cancer cells

Cyril Corbet (), Estelle Bastien, Joao Pedro Santiago de Jesus, Emeline Dierge, Ruben Martherus, Catherine Vander Linden, Bastien Doix, Charline Degavre, Céline Guilbaud, Laurenne Petit, Carine Michiels, Chantal Dessy, Yvan Larondelle and Olivier Feron ()
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Cyril Corbet: UCLouvain
Estelle Bastien: UCLouvain
Joao Pedro Santiago de Jesus: UCLouvain
Emeline Dierge: UCLouvain
Ruben Martherus: UCLouvain
Catherine Vander Linden: UCLouvain
Bastien Doix: UCLouvain
Charline Degavre: UCLouvain
Céline Guilbaud: UCLouvain
Laurenne Petit: UCLouvain
Carine Michiels: University of Namur
Chantal Dessy: UCLouvain
Yvan Larondelle: UCLouvain
Olivier Feron: UCLouvain

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: Abstract Acidosis, a common characteristic of the tumor microenvironment, is associated with alterations in metabolic preferences of cancer cells and progression of the disease. Here we identify the TGF-β2 isoform at the interface between these observations. We document that acidic pH promotes autocrine TGF-β2 signaling, which in turn favors the formation of lipid droplets (LD) that represent energy stores readily available to support anoikis resistance and cancer cell invasiveness. We find that, in cancer cells of various origins, acidosis-induced TGF-β2 activation promotes both partial epithelial-to-mesenchymal transition (EMT) and fatty acid metabolism, the latter supporting Smad2 acetylation. We show that upon TGF-β2 stimulation, PKC-zeta-mediated translocation of CD36 facilitates the uptake of fatty acids that are either stored as triglycerides in LD through DGAT1 or oxidized to generate ATP to fulfill immediate cellular needs. We also address how, by preventing fatty acid mobilization from LD, distant metastatic spreading may be inhibited.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-14262-3

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DOI: 10.1038/s41467-019-14262-3

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