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

被引：14
|
作者：
Hou, Xiaodan [1 ,3 ]
Zhang, Jieying [1 ]
Wang, Yongbin [1 ]
Xiong, Wujun [2 ]
Mi, Jun [1 ]
机构：
[1] Shanghai Jiao Tong Univ, Sch Med, Shanghai Key Lab Tumor Microenvironm & Inflammat, Dept Biochem & Mol Cell Biol, Shanghai, Peoples R China
[2] Tongji Univ, Shanghai East Hosp, Shanghai, Peoples R China
[3] Chinese Acad Med Sci, Suzhou Inst Syst Med, Ctr Syst Med, Beijing, Peoples R China
来源：
ONCOTARGET | 2017年 / 8卷 / 48期
基金：
美国国家科学基金会;
关键词：
IDH1; TGFBR; TGF-beta signalling; Cav1; alpha-ketoglutarate; CELLULAR-RESPONSES; I RECEPTOR; HISTONE H3; CAVEOLIN-1; CELLS; EXPRESSION; PROTEINS; LYSINE-9; COMPLEX; FAMILY;
D O I：
10.18632/oncotarget.20861
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
TGF-beta signalling plays an important role in fibroblasts activation and tumour progression. Here, we report that the TGFBR-IDH1-Cav1 axis promotes TGF-beta signalling in fibroblasts. Our data demonstrated that IDH1 was downregulated by TGF-beta signalling in fibroblasts, and downregulation of IDH1 increased cellular concentration of alpha-ketoglutarate (alpha-KG) by accelerating glutamine metabolization. Interestingly, alpha-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-beta signalling. These findings demonstrated that metabolic enzyme IDH1 regulates TGF-beta signalling by feedback mechanism through alpha-KG and TGFBR-IDH1-Cav1 axis is important for TGF-beta signalling.
引用
收藏
页码：83962 / 83974
页数：13
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