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, Olivier Feron

Résultats de recherche: Contribution à un journal/une revueArticle

Résumé

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.

langue originaleAnglais
Numéro d'article454
Pages (de - à)454
Nombre de pages15
journalNature Communications
Volume11
Numéro de publication1
Les DOIs
Etat de la publicationPublié - 23 janv. 2020
Modification externeOui

Empreinte digitale Examiner les sujets de recherche de « TGFβ2-induced formation of lipid droplets supports acidosis-driven EMT and the metastatic spreading of cancer cells ». Ensemble, ils forment une empreinte digitale unique.

  • Équipement

  • Morphologie - Imagerie

    Charles Nicaise (!!Manager) & Francesca Cecchet (!!Manager)

    Plateforme technologique Morphologie, imagerie

    Equipement/installations: Plateforme technolgique

  • Contient cette citation

    Corbet, C., Bastien, E., Santiago de Jesus, J. P., Dierge, E., Martherus, R., Vander Linden, C., Doix, B., Degavre, C., Guilbaud, C., Petit, L., Michiels, C., Dessy, C., Larondelle, Y., & Feron, O. (2020). TGFβ2-induced formation of lipid droplets supports acidosis-driven EMT and the metastatic spreading of cancer cells. Nature Communications, 11(1), 454. [454]. https://doi.org/10.1038/s41467-019-14262-3