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
相关论文
共 50 条
  • [1] TGF-β1 promotes bovine mammary fibroblast proliferation through the ERK 1/2 signalling pathway
    Gao, Yuanyuan
    Wang, Yuping
    Li, Yingying
    Xia, Xiaojing
    Zhao, Shuang
    Che, Yanyi
    Sun, Yingying
    Lei, Liancheng
    CELL BIOLOGY INTERNATIONAL, 2016, 40 (07) : 750 - 760
  • [2] A miRNA-145/TGF-β1 negative feedback loop regulates the cancer-associated fibroblast phenotype
    Melling, Genevieve E.
    Flannery, Sarah E.
    Abidin, Siti A.
    Clemmens, Hannah
    Prajapati, Priyanka
    Hinsley, Emma E.
    Hunt, Stuart
    Catto, James W. F.
    Della Coletta, Ricardo
    Mellone, Massimiliano
    Thomas, Gareth J.
    Parkinson, E. Ken
    Prime, Stephen S.
    Paterson, Ian C.
    Buttle, David J.
    Lambert, Daniel W.
    CARCINOGENESIS, 2018, 39 (06) : 798 - 807
  • [3] Pancreatic cancer-associated retinoblastoma 1 dysfunction enables TGF-β to promote proliferation
    Gore, A. Jesse
    Deitz, Samantha L.
    Palam, Lakshmi Reddy
    Craven, Kelly E.
    Korc, Murray
    JOURNAL OF CLINICAL INVESTIGATION, 2014, 124 (01) : 338 - 352
  • [4] Chemokine switch regulated by TGF-β1 in cancer-associated fibroblast subsets determines the efficacy of chemo-immunotherapy
    Vienot, Angelique
    Pallandre, Jean-Rene
    Renaude, Elodie
    Viot, Julien
    Bouard, Adeline
    Spehner, Laurie
    Kroemer, Marie
    Abdeljaoued, Syrine
    van der Woning, Bas
    de Haard, Hans
    Loyon, Romain
    Hervouet, Eric
    Peixoto, Paul
    Borg, Christophe
    ONCOIMMUNOLOGY, 2022, 11 (01):
  • [5] Dualism of FGF and TGF-β Signaling in Heterogeneous Cancer-Associated Fibroblast Activation with ETV1 as a Critical Determinant
    Bordignon, Pino
    Bottoni, Giulia
    Xu, Xiaoying
    Popescu, Alma S.
    Truan, Zinnia
    Guenova, Emmanuella
    Kofler, Lukas
    Jafari, Paris
    Ostano, Paola
    Roecken, Martin
    Neel, Victor
    Dotto, G. Paolo
    CELL REPORTS, 2019, 28 (09): : 2358 - +
  • [6] PPARδ promotes oncogenic redirection of TGF-β1 signaling through the activation of the ABCA1-Cav1 pathway
    Her, Nam-Gu
    Jeong, Seong-In
    Cho, Kyucheol
    Ha, Tae-Kyu
    Han, Jikhyon
    Ko, Kyung-Phil
    Park, Soon-Ki
    Lee, Jin-Hee
    Lee, Min-Goo
    Ryu, Byung-Kyu
    Chi, Sung-Gil
    CELL CYCLE, 2013, 12 (10) : 1521 - 1535
  • [7] Cancer-associated fibroblast-derived Gremlin 1 promotes breast cancer progression
    Ren, Jiang
    Smid, Marcel
    Iaria, Josephine
    Salvatori, Daniela C. F.
    van Dam, Hans
    Zhu, Hong Jian
    Martens, John W. M.
    ten Dijke, Peter
    BREAST CANCER RESEARCH, 2019, 21 (01)
  • [8] RETRACTED: MiR-151-3p transferred by cancer-associated fibroblast-derived extracellular vesicles promotes osteosarcoma progression through the CHL1/integrin 1β/TGF-β axis (Retracted Article)
    Wang, Peng
    Wang, Changchao
    Zhu, Leyin
    Li, Ping
    Tang, Xiaobo
    Wang, Jian
    Hu, Fangyong
    Qiao, Gaoshan
    Xie, Cheng
    Zhu, Chengdong
    CANCER GENE THERAPY, 2021, 28 (12) : 1390 - 1390
  • [9] MKRN1 promotes colorectal cancer metastasis by activating the TGF-β signalling pathway through SNIP1 protein degradation
    Zhang, Yi
    Li, Qin-shan
    Liu, Hong-lin
    Tang, Hong-ting
    Yang, Han-lin
    Wu, Dao-qiu
    Huang, Yu-ying
    Li, Li-cheng
    Liu, Li-hong
    Li, Meng-xing
    JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2023, 42 (01)
  • [10] Ethanol promotes alcohol-related colorectal cancer metastasis via the TGF-β/RUNX3/Snail axis by inducing TGF-β1 upregulation and RUNX3 cytoplasmic mislocalization
    Zheng, Kehong
    Yu, Jinlong
    Chen, Zetao
    Zhou, Rui
    Lin, Chuang
    Zhang, Yuxuan
    Huang, Zonghai
    Yu, Lina
    Zhao, Liang
    Wang, Qian
    EBIOMEDICINE, 2019, 50 : 224 - 237
12345