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Adipocytes promote breast tumorigenesis through TAZ-dependent secretion of Resistin.
Gao, Yuhao; Chen, Xiaosong; He, Qing; Gimple, Ryan C; Liao, Yajin; Wang, Liang; Wu, Rong; Xie, Qi; Rich, Jeremy N; Shen, Kunwei; Yuan, Zengqiang.
Affiliation
  • Gao Y; The Brain Science Center, Beijing Institute of Basic Medical Sciences, 100850 Beijing, China.
  • Chen X; Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
  • He Q; Department of Biochemistry and Molecular and Cell Biology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
  • Gimple RC; The Brain Science Center, Beijing Institute of Basic Medical Sciences, 100850 Beijing, China.
  • Liao Y; Department of Medicine, Division of Regenerative Medicine, University of California, San Diego, La Jolla, CA 92037.
  • Wang L; Department of Pathology, Case Western Reserve University, Cleveland, OH 44120.
  • Wu R; The Brain Science Center, Beijing Institute of Basic Medical Sciences, 100850 Beijing, China.
  • Xie Q; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Center for Influenza Research and Early-Warning (CASCIRE), Chinese Academy of Sciences, 100101 Beijing, China.
  • Rich JN; The Brain Science Center, Beijing Institute of Basic Medical Sciences, 100850 Beijing, China.
  • Shen K; School of Life Sciences, Westlake University, 310024 Hangzhou, Zhejiang, China.
  • Yuan Z; Department of Medicine, Division of Regenerative Medicine, University of California, San Diego, La Jolla, CA 92037; drjeremyrich@gmail.com kwshen@medmail.com.cn zyuan620@yahoo.com.
Proc Natl Acad Sci U S A ; 117(52): 33295-33304, 2020 12 29.
Article de En | MEDLINE | ID: mdl-33318171
Adipocytes have been implicated in breast tumor growth and stemness maintenance through secreted factors. However, the mechanisms by which these cytokines are regulated during diet-induced obesity and contribute to breast tumorigenesis remain largely unknown. Here we show that transcription cofactor TAZ in adipocytes is directly up-regulated by the free fatty acid/PPARγ axis upon dietary fat stimulation. TAZ knockdown alters the expression profile of a series of secreted proteins and attenuates the tumor-supporting function of adipocytes. Moreover, we identify Resistin, an adipose-derived hormone, as a functional downstream target of TAZ, which facilitates tumorigenesis, and its expression correlated with adipocyitc TAZ in triple-negative breast cancer samples. Further, Adiponectin-cre-mediated TAZ knockout in adipocytes mitigates breast tumor growth. Taken together, our findings highlight how diet-induced TAZ expression in adipocytes promotes tumorigenesis, suggesting promising cancer therapeutic targets.
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Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Tumeurs du sein / Transactivateurs / Adipocytes / Résistine / Carcinogenèse Type d'étude: Prognostic_studies Limites: Animals / Female / Humans Langue: En Journal: Proc Natl Acad Sci U S A Année: 2020 Type de document: Article Pays d'affiliation: Chine Pays de publication: États-Unis d'Amérique

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Tumeurs du sein / Transactivateurs / Adipocytes / Résistine / Carcinogenèse Type d'étude: Prognostic_studies Limites: Animals / Female / Humans Langue: En Journal: Proc Natl Acad Sci U S A Année: 2020 Type de document: Article Pays d'affiliation: Chine Pays de publication: États-Unis d'Amérique