title: Complement proteins C7 and CFH control the stemness of liver cancer cells via LSF-1.
abstract: Tumor-initiating cells are important for the formation and maintenance of tumor bulks in various tumors. To identify surface markers of liver tumor-initiating cells, we performed primary tumorsphere culture and analyzed the expression of cluster of differentiation (CD) antigen genes using NanoString. Interestingly, we found significant upregulation of the complement proteins (p = 1.60 × 10(-18)), including C7 and CFH. Further studies revealed that C7 and CFH are required to maintain stemness in liver cancer cells. Knockdown of C7 and CFH expression abrogated tumorsphere formation and induced differentiation, whereas overexpression stimulated stemness factor expression as well as in vivo cell growth. Mechanistically, by studying C7 and CFH-dependent LSF-1 expression and its direct role on stemness factor transcription, we found that LSF-1 is involved in this regulation. Taken together, our data demonstrate the unprecedented role of complement proteins on the maintenance of stemness in liver tumor-initiating cells.
authors.affiliation: Asan Institute for Life Science, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Hyang Sook
authors.initials: HS
authors.lastname: Seol
authors.affiliation: Asan Institute for Life Science, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Sang Eun
authors.initials: SE
authors.lastname: Lee
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Joon Seon
authors.initials: JS
authors.lastname: Song
authors.affiliation: Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Je-Keun
authors.initials: JK
authors.lastname: Rhee
authors.affiliation: Basic Research Laboratory, Stem Cell Regulation and Animal Aging Section, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.
authors.forename: Shree Ram
authors.initials: SR
authors.lastname: Singh
authors.affiliation: Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. Electronic address: suhwan.chang@amc.seoul.kr.
authors.forename: Suhwan
authors.initials: S
authors.lastname: Chang
authors.affiliation: Asan Institute for Life Science, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. Electronic address: jangsejin@amc.seoul.kr.
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Jang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003184:Complement C7 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D017242:Complement Factor H / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D007113:Immunity, Innate; D008113:Liver Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D034622:RNA Interference; D015398:Signal Transduction; D018874:Spheroids, Cellular; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D047368:Tumor Burden; D014407:Tumor Cells, Cultured
chemical_list: C493495:CFH protein, human; D003184:Complement C7; D004268:DNA-Binding Proteins; C501906:TFCP2 protein, human; D014157:Transcription Factors; D017242:Complement Factor H
keywords: CFH; Complement protein C7; HCC; LSF-1; Liver tumor-initiating cell; Stemness factor