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

Xiaodan Hou; Jieying Zhang; Yongbin Wang; Wujun Xiong; Jun Mi

doi:10.18632/oncotarget.20861

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Research Papers:

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

Xiaodan Hou, Jieying Zhang, Yongbin Wang, Wujun Xiong and Jun Mi _

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Oncotarget. 2017; 8:83962-83974. https://doi.org/10.18632/oncotarget.20861

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Abstract

Xiaodan Hou1,3, Jieying Zhang1, Yongbin Wang1, Wujun Xiong2 and Jun Mi1

1Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China

2Shanghai East Hospital, Affiliated to Tongji University, Shanghai, China

3Center of Systems Medicine, Chinese Academy of Medical Sciences, Suzhou Institute of Systems Medicine, Suzhou, China

Correspondence to:

Jun Mi, email: [email protected]

Wujun Xiong, email: [email protected]

Keywords: IDH1, TGFBR, TGF-β signalling, Cav1, alpha-ketoglutarate

Received: July 28, 2017 Accepted: August 23, 2017 Published: September 13, 2017

ABSTRACT

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. Furthermore, Cav1 downregulation inhibited TGFBR protein degradation. In turn, the activated TGFBR promoted TGF-β signalling. These findings demonstrated that metabolic enzyme IDH1 regulates TGF-β signalling by feedback mechanism through α-KG and TGFBR-IDH1-Cav1 axis is important for TGF-β signalling.

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Research Papers:

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

Abstract