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
  • [41] Netrin G1 Promotes Pancreatic Tumorigenesis through Cancer-Associated Fibroblast-Driven Nutritional Support and Immunosuppression
    Francescone, Ralph
    Vendramini-Costa, Debora Barbosa
    Franco-Barraza, Janusz
    Wagner, Jessica
    Muir, Alexander
    Lau, Allison N.
    Gabitova, Linara
    Pazina, Tatiana
    Gupta, Sapna
    Luong, Tiffany
    Rollins, Dustin
    Malik, Ruchi
    Thapa, Roshan J.
    Restifo, Diana
    Zhou, Yan
    Cai, Kathy Q.
    Hensley, Harvey H.
    Tan, Yinfei
    Kruger, Warren D.
    Devarajan, Karthik
    Balachandran, Siddharth
    Klein-Szanto, Andres J.
    Wang, Huamin
    El-Deiry, Wafik S.
    Vander Heiden, Matthew G.
    Peri, Suraj
    Campbell, Kerry S.
    Astsaturov, Igor
    Cukierman, Edna
    CANCER DISCOVERY, 2021, 11 (02) : 446 - 479
  • [42] BATF promotes extramedullary infiltration through TGF-β1/Smad/MMPs axis in acute myeloid leukemia
    Zhang, Ru
    Miao, Jiyu
    Zhai, Meng
    Liu, Rui
    Li, Fangmei
    Xu, Xuezhu
    Huang, Lingjuan
    Wang, Ting
    Yang, Rui
    Yang, Ruoyu
    Wang, Yiwen
    He, Aili
    Wang, Jianli
    MOLECULAR CARCINOGENESIS, 2024, 63 (06) : 1146 - 1159
  • [43] Cancer-associated fibroblast-secreted exosomal miR-423-5p promotes chemotherapy resistance in prostate cancer by targeting GREM2 through the TGF-β signaling pathway
    Shan, Guang
    Gu, Juan
    Zhou, Daoping
    Li, Lingxun
    Cheng, Wei
    Wang, Yueping
    Tang, Tian
    Wang, Xuedong
    EXPERIMENTAL AND MOLECULAR MEDICINE, 2020, 52 (11) : 1809 - 1822
  • [44] Chondroitin polymerizing factor predicts a poor prognosis and promotes breast cancer progression via the upstream TGF-β1/SMAD3 and JNK axis activation
    Pan, Qiang-Feng
    Ouyang, Wei-Wei
    Zhang, Meng-Qi
    He, Shuo
    Yang, Si-Yun
    Zhang, Jun
    JOURNAL OF CELL COMMUNICATION AND SIGNALING, 2023, 17 (01) : 89 - 102
  • [45] Silencing DACH1 Promotes Esophageal Cancer Growth by Inhibiting TGF-β Signaling
    Wu, Liang
    Herman, James G.
    Brock, Malcolm V.
    Wu, Kongming
    Mao, Gaoping
    Yan, Wenji
    Nie, Yan
    Liang, Hao
    Zhan, Qimin
    Li, Wen
    Guo, Mingzhou
    PLOS ONE, 2014, 9 (04):
  • [46] TGF-β1 stimulates epithelial-mesenchymal transition and cancer-associated myoepithelial cell during the progression from in situ to invasive breast cancer
    Wang, Li
    Xu, Cong
    Liu, Xia
    Yang, Yang
    Cao, Lu
    Xiang, Guomin
    Liu, Fang
    Wang, Shuling
    Liu, Jing
    Meng, Qingxiang
    Jiao, Jiao
    Niu, Yun
    CANCER CELL INTERNATIONAL, 2019, 19 (01)
  • [47] ITGBL1 promotes cell migration and invasion through stimulating the TGF-β signalling pathway in hepatocellular carcinoma
    Huang, Wei
    Yu, Demin
    Wang, Mingjie
    Han, Yue
    Lin, Junyu
    Wei, Dong
    Cai, Jialin
    Li, Bin
    Chen, Peizhan
    Zhang, Xinxin
    CELL PROLIFERATION, 2020, 53 (07)
  • [48] Hypermethylation of the TGF-β target, ABCA1 is associated with poor prognosis in ovarian cancer patients
    Chou, Jian-Liang
    Huang, Rui-Lan
    Shay, Jacqueline
    Chen, Lin-Yu
    Lin, Sheng-Jie
    Yan, Pearlly S.
    Chao, Wei-Ting
    Lai, Yi-Hui
    Lai, Yen-Ling
    Chao, Tai-Kuang
    Lee, Cheng-I
    Tai, Chien-Kuo
    Wu, Shu-Fen
    Nephew, Kenneth P.
    Huang, Tim H-M
    Lai, Hung-Cheng
    Chan, Michael W. Y.
    CLINICAL EPIGENETICS, 2015, 7
  • [49] Crosstalk between oral squamous cell carcinoma cells and cancer-associated fibroblasts via the TGF-β/SOX9 axis in cancer progression
    Haga, Kenta
    Yamazaki, Manabu
    Maruyama, Satoshi
    Kawaharada, Masami
    Suzuki, Ayako
    Hoshikawa, Emi
    Chan, Nyein Nyein
    Funayama, Akinori
    Mikami, Toshihiko
    Kobayashi, Tadaharu
    Izumi, Kenji
    Tanuma, Jun-ichi
    TRANSLATIONAL ONCOLOGY, 2021, 14 (12):
  • [50] TGF-β1 promotes transition of mesothelial cells into fibroblast phenotype in response to peritoneal injury in a cell culture model
    Falk, Peter
    Angenete, Eva
    Bergstrom, Maria
    Ivarsson, Marie-Lois
    INTERNATIONAL JOURNAL OF SURGERY, 2013, 11 (09) : 977 - 982
12345