作者
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
发表日期
2020/1/23
期刊
Nature communications
卷号
11
期号
1
页码范围
454
出版商
Nature Publishing Group UK
简介
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 …
引用总数
学术搜索中的文章