title: CD59 Regulation by SOX2 Is Required for Epithelial Cancer Stem Cells to Evade Complement Surveillance.
abstract: Cancer stem cells (CSCs) are highly associated with therapy resistance and metastasis. Interplay between CSCs and various immune components is required for tumor survival. However, the response of CSCs to complement surveillance remains unknown. Herein, using stem-like sphere-forming cells prepared from a mammary tumor and a lung adenocarcinoma cell line, we found that CD59 was upregulated to protect CSCs from complement-dependent cytotoxicity. CD59 silencing significantly enhanced complement destruction and completely suppressed tumorigenesis in CSC-xenografted nude mice. Furthermore, we identified that SOX2 upregulates CD59 in epithelial CSCs. In addition, we revealed that SOX2 regulates the transcription of mCd59b, leading to selective mCD59b abundance in murine testis spermatogonial stem cells. Therefore, we demonstrated that CD59 regulation by SOX2 is required for stem cell evasion of complement surveillance. This finding highlights the importance of complement surveillance in eliminating CSCs and may suggest CD59 as a potential target for cancer therapy.
authors.affiliation: Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Collaborative Innovation Center of Cancer Medicine, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai 200032, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Chen
authors.affiliation: Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Collaborative Innovation Center of Cancer Medicine, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai 200032, China.
authors.forename: Peipei
authors.initials: P
authors.lastname: Ding
authors.affiliation: Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Collaborative Innovation Center of Cancer Medicine, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai 200032, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.affiliation: Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Collaborative Innovation Center of Cancer Medicine, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai 200032, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Gu
authors.affiliation: Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Collaborative Innovation Center of Cancer Medicine, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai 200032, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Collaborative Innovation Center of Cancer Medicine, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai 200032, China.
authors.forename: Long
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Collaborative Innovation Center of Cancer Medicine, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai 200032, China.
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.affiliation: Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Collaborative Innovation Center of Cancer Medicine, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai 200032, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Gan
authors.affiliation: Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Collaborative Innovation Center of Cancer Medicine, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai 200032, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Collaborative Innovation Center of Cancer Medicine, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai 200032, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Collaborative Innovation Center of Cancer Medicine, Shanghai Medical College, Fudan University, 270 Dong'an Road, Shanghai 200032, China; Department of Immunology, Shanghai Medical College, Fudan University, 130 Dong'an Road, Shanghai 200032, China. Electronic address: weiguohu@fudan.edu.cn.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Hu
mesh_terms: D000818:Animals; D000074322:Antineoplastic Agents, Immunological / Q000494:pharmacology; D018957:CD59 Antigens / Q000235:genetics* / Q000378:metabolism; D063646:Carcinogenesis; D002277:Carcinoma / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D000068818:Cetuximab / Q000494:pharmacology; D003165:Complement System Proteins / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D007157:Immunologic Surveillance; D008297:Male; D051379:Mice; D014411:Neoplastic Stem Cells / Q000276:immunology / Q000378:metabolism*; D055748:SOXB1 Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D019139:Tumor Escape / Q000235:genetics / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000074322:Antineoplastic Agents, Immunological; D018957:CD59 Antigens; D055748:SOXB1 Transcription Factors; D003165:Complement System Proteins; D000068818:Cetuximab
keywords: CD59; SOX2; complement surveillance; complement-dependent cytotoxity; mCD59a; mCD5b; mouse testis; stem cells; transcription regulation