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TGFBR-IDH1-Cav1 axis promotes TGF-? signalling in cancer-associated fibroblast.

ABSTRACT: TGF-? signalling plays an important role in fibroblasts activation and tumour progression. Here, we report that the TGFBR-IDH1-Cav1 axis promotes TGF- ? signalling in fibroblasts. Our data demonstrated that IDH1 was downregulated by TGF-? signalling in fibroblasts, and downregulation of IDH1 increased cellular concentration of ?-ketoglutarate (?-KG) by accelerating glutamine metabolization. Interestingly, ?-KG suppressed Cav1 expression through reducing the trimethylation of histone H3K4. Furthermore, Cav1 downregulation inhibited TGFBR protein degradation. In turn, the activated TGFBR promoted TGF-? signalling. These findings demonstrated that metabolic enzyme IDH1 regulates TGF-? signalling by feedback mechanism through ?-KG and TGFBR-IDH1-Cav1 axis is important for TGF-? signalling.

SUBMITTER: Hou X

PROVIDER: S-EPMC5663568 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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TGFBR-IDH1-Cav1 axis promotes TGF-β signalling in cancer-associated fibroblast.

Hou Xiaodan X Zhang Jieying J Wang Yongbin Y Xiong Wujun W Mi Jun J

Oncotarget 20170913 48

TGF-β signalling plays an important role in fibroblasts activation and tumour progression. Here, we report that the TGFBR-IDH1-Cav1 axis promotes TGF- β signalling in fibroblasts. Our data demonstrated that IDH1 was downregulated by TGF-β signalling in fibroblasts, and downregulation of IDH1 increased cellular concentration of α-ketoglutarate (α-KG) by accelerating glutamine metabolization. Interestingly, α-KG suppressed Cav1 expression through reducing the trimethylation of histone H3K4. Furthe ...[more]

PMID: 29137396

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