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Human iPSC-based breast cancer model identifies S100P-dependent cancer stemness induced by BRCA1 mutation

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机构: [1]Sun Yat Sen Univ, Affiliated Hosp 7, Zhongshan Sch Med, Dept Rehabil Med, Shenzhen 518107, Guangdong, Peoples R China [2]Xuzhou Med Univ, Canc Inst, Xuzhou 221002, Jiangsu, Peoples R China [3]Sichuan Univ, West China Hosp 2,West China Biomed Big Data Ctr, Dept Gynecol & Obstet,West China Sch Med, West China Hosp,Tianfu Jincheng Lab,Frontiers Med, Chengdu 610041, Peoples R China [4]Sun Yat Sen Univ, Affiliated Hosp 1,Sch Basic Med Sci,Ctr Stem Cell, Guangdong Med Univ,Key Lab Stem Cells & Tissue En, Minist Educ,Zhongshan Sch Med,Adv Med Technol Ctr, Guangzhou, Guangdong, Peoples R China [5]Sun Yat Sen Univ, Affiliated Hosp 3, Vaccine Res Inst, Guangzhou 510630, Peoples R China [6]Guangzhou Natl Lab, Guangzhou 510005, Peoples R China [7]Southern Med Univ, Shenzhen Eye Hosp, Shenzhen Eye Med Ctr, 18 Zetian Rd, Shenzhen 518040, Peoples R China [8]Sunshine Lake Pharm Co Ltd, Dongguan 523871, Peoples R China [9]Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Oncol, Guangzhou 510120, Peoples R China [10]Sun Yat Sen Univ, Zhongshan Sch Med, Key Lab Stem Cells & Tissue Engn, Minist Educ, Guangzhou 510080, Peoples R China [11]Chinese Acad Sci, Ctr Excellence Mol Cell Sci, State Key Lab Cell Biol, Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China [12]Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai 200031, Peoples R China [13]Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Breast Tumor Ctr, Guangzhou 510120, Peoples R China [14]Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Guangdong Prov Key Lab Malignant Tumor Epigenet &, Guangzhou 510120, Peoples R China [15]Guangzhou Med Univ, Sch Basic Med Sci, Guangzhou 511436, Peoples R China [16]Univ Santiago De Compostela USC, Hlth Res Inst IDIS, Ctr Res Mol Med & Chron Dis CiMUS, Santiago De Compostela 15782, Spain [17]Sun Yat Sen Univ, Affiliated Hosp 1, Dept Breast & Thyroid Surg, Guangzhou 510275, Peoples R China [18]Sun Yat Sen Univ, Zhongshan Sch Med, Dept Immunol, Guangzhou 510080, Peoples R China [19]Univ Texas Hlth Sci Ctr Houston, McGovern Med Sch, Dept Integrat Biol & Pharmacol, Houston, TX 77030 USA [20]Univ Texas MD Anderson Canc Ctr, UTHlth Grad Sch Biomed Sci, Houston, TX 77030 USA [21]Sun Yat Sen Univ, Canc Ctr, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China, Guangzhou 510060, Peoples R China [22]Guangzhou Med Univ, Affiliated Hosp 1, State Key Lab Resp Dis, Guangzhou 510120, Peoples R China
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Breast cancer is the most common malignancy in females and remains the leading cause of cancer-related deaths for women worldwide. The cellular and molecular basis of breast tumorigenesis is not completely understood partly due to the lack of human research models which simulate the development of breast cancer. Here, we developed a method for generating functional mammary-like cells (MCs) from human-induced pluripotent stem cells (iPSCs). The iPSC-MCs closely resemble human primary MCs at cellular, transcriptional, and functional levels. Using this method, a breast cancer model was generated using patient-derived iPSCs harboring germline BRCA1 mutation. The patient iPSC-MCs recapitulated the transcriptome, clinical genomic alteration, and tumorigenic ability of breast cancer cells. We also identified S100P as an oncogene downstream of mutated BRCA1 that promotes cancer cell stemness and tumorigenesis. Our study establishes a promising system of breast cancer for studying the mechanism of tumorigenesis and identifying potential therapeutic targets.

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大类 | 1 区 综合性期刊
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Q1 MULTIDISCIPLINARY SCIENCES
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Q1 MULTIDISCIPLINARY SCIENCES

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第一作者:
第一作者机构: [1]Sun Yat Sen Univ, Affiliated Hosp 7, Zhongshan Sch Med, Dept Rehabil Med, Shenzhen 518107, Guangdong, Peoples R China [2]Xuzhou Med Univ, Canc Inst, Xuzhou 221002, Jiangsu, Peoples R China [3]Sichuan Univ, West China Hosp 2,West China Biomed Big Data Ctr, Dept Gynecol & Obstet,West China Sch Med, West China Hosp,Tianfu Jincheng Lab,Frontiers Med, Chengdu 610041, Peoples R China [4]Sun Yat Sen Univ, Affiliated Hosp 1,Sch Basic Med Sci,Ctr Stem Cell, Guangdong Med Univ,Key Lab Stem Cells & Tissue En, Minist Educ,Zhongshan Sch Med,Adv Med Technol Ctr, Guangzhou, Guangdong, Peoples R China [5]Sun Yat Sen Univ, Affiliated Hosp 3, Vaccine Res Inst, Guangzhou 510630, Peoples R China [6]Guangzhou Natl Lab, Guangzhou 510005, Peoples R China [7]Southern Med Univ, Shenzhen Eye Hosp, Shenzhen Eye Med Ctr, 18 Zetian Rd, Shenzhen 518040, Peoples R China
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通讯机构: [1]Sun Yat Sen Univ, Affiliated Hosp 7, Zhongshan Sch Med, Dept Rehabil Med, Shenzhen 518107, Guangdong, Peoples R China [2]Xuzhou Med Univ, Canc Inst, Xuzhou 221002, Jiangsu, Peoples R China [3]Sichuan Univ, West China Hosp 2,West China Biomed Big Data Ctr, Dept Gynecol & Obstet,West China Sch Med, West China Hosp,Tianfu Jincheng Lab,Frontiers Med, Chengdu 610041, Peoples R China [4]Sun Yat Sen Univ, Affiliated Hosp 1,Sch Basic Med Sci,Ctr Stem Cell, Guangdong Med Univ,Key Lab Stem Cells & Tissue En, Minist Educ,Zhongshan Sch Med,Adv Med Technol Ctr, Guangzhou, Guangdong, Peoples R China [6]Guangzhou Natl Lab, Guangzhou 510005, Peoples R China [7]Southern Med Univ, Shenzhen Eye Hosp, Shenzhen Eye Med Ctr, 18 Zetian Rd, Shenzhen 518040, Peoples R China [22]Guangzhou Med Univ, Affiliated Hosp 1, State Key Lab Resp Dis, Guangzhou 510120, Peoples R China
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