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Antiandrogen treatment induces stromal cell reprogramming to promote castration resistance in cancer

文献类型：期刊论文

作者Wang, Hanling1,2; Li, Ni1,2; Liu, Qiuli3; Guo, Jiacheng1,2; Pan, Qiang1,2; Cheng, Bisheng4; Xu, Junyu5; Dong, Baijun6; Yang, Guanjie7; Yang, Bin7
刊名CANCER CELL
出版日期2023-07-10
卷号41期号:7页码:1345-+
ISSN号1535-6108
DOI10.1016/j.ccell.2023.05.016
通讯作者Jiang, Jun(jiangjun_64@163.com) ; Huang, Hai(huangh9@mail.sysu.edu.cn) ; Qin, Jun(jiangjun_64@163.com)
英文摘要Lineage plasticity causes therapeutic resistance; however, it remains unclear how the fate conversion and phenotype switching of cancer-associated fibroblasts (CAFs) are implicated in disease relapse. Here, we show that androgen deprivation therapy (ADT)-induced SPP1+ myofibroblastic CAFs (myCAFs) are critical stromal constituents that drive the development of castration-resistant prostate cancer (CRPC). Our results reveal that SPP1+ myCAFs arise from the inflammatory CAFs in hormone-sensitive PCa; therefore, they represent two functional states of an otherwise ontogenically identical cell type. Antiandrogen treatment un-leashes TGF-b signaling, resulting in SOX4-SWI/SNF-dependent CAF phenotype switching. SPP1+ myCAFs in turn render PCa refractory to ADT via an SPP1-ERK paracrine mechanism. Importantly, these sub-myCAFs are associated with inferior therapeutic outcomes, providing the rationale for inhibiting polarization or para-crine mechanisms to circumvent castration resistance. Collectively, our results highlight that therapy -induced phenotypic switching of CAFs is coupled with disease progression and that targeting this stromal component may restrain CRPC.
WOS关键词SET ENRICHMENT ANALYSIS ; DRIVES IMMUNE EVASION ; PROSTATE-CANCER ; WEB SERVER ; TGF-BETA ; MECHANISMS ; FIBROBLASTS ; METASTASIS ; MUTATIONS ; MOUSE
资助项目National Key Research and Development Program of China[2021YFA1300601] ; National Key Research and Development Program of China[2018YFA0902700] ; National Natural Science Foundation of China Projects[82341012] ; National Natural Science Foundation of China Projects[81825018] ; National Natural Science Foundation of China Projects[82130085] ; National Natural Science Foundation of China Projects[82203495] ; National Natural Science Foundation of China Projects[81974395] ; National Natural Science Foundation of China Projects[82173036] ; Shanghai Pilot Program for Basic Research -Chinese Academy of Sciences, Shanghai Branch[JCYJ-SHFY-2022-007] ; Innovative research team of high-level local universities in Shanghai, China ; Youth Innovation Promotion Association of CAS, China ; NovelBio Co., Ltd.
WOS研究方向Oncology ; Cell Biology
语种英语
出版者CELL PRESS
WOS记录号WOS:001040059500001
源URL[http://119.78.100.183/handle/2S10ELR8/306818]  
专题新药研究国家重点实验室
通讯作者Jiang, Jun; Huang, Hai; Qin, Jun
作者单位1.Shanghai Jiao Tong Univ Sch Med SJTUSM, Shanghai Inst Nutr & Hlth, CAS Ctr Excellence Mol Cell Sci, CAS Key Lab Tissue Microenvironm & Tumor, 320 Yueyang Rd, Shanghai 200031, Peoples R China
2.Chinese Acad Sci, 320 Yueyang Rd, Shanghai 200031, Peoples R China
3.Army Med Univ, Daping Hosp, Inst Surg Res, Dept Urol, Chongqing 400042, Peoples R China
4.Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Urol, Guangzhou 510120, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
6.Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Dept Urol, Shanghai 200127, Peoples R China
7.Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Urol, 301 Yanchang Rd, Shanghai 200072, Peoples R China
8.Sichuan Univ, West China Univ Hosp 2, Dept Obstet Gynecol & Pediat, 20 Renmin South Rd, Chengdu 610041, Peoples R China
9.Nanjing Med Univ, Collaborat Innovat Ctr Canc Personalized Med, 101 Longmian Ave, Nanjing 211166, Jiangsu, Peoples R China
10.China Agr Univ, Coll Biol Sci, State Key Labs Agrobiotechnol, Beijing 100193, Peoples R China
推荐引用方式
GB/T 7714		 Wang, Hanling,Li, Ni,Liu, Qiuli,et al. Antiandrogen treatment induces stromal cell reprogramming to promote castration resistance in cancer[J]. CANCER CELL,2023,41(7):1345-+.
APA Wang, Hanling.,Li, Ni.,Liu, Qiuli.,Guo, Jiacheng.,Pan, Qiang.,...&Qin, Jun.(2023).Antiandrogen treatment induces stromal cell reprogramming to promote castration resistance in cancer.CANCER CELL,41(7),1345-+.
MLA Wang, Hanling,et al."Antiandrogen treatment induces stromal cell reprogramming to promote castration resistance in cancer".CANCER CELL 41.7(2023):1345-+.

入库方式： OAI收割

来源：上海药物研究所

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