title: CD24(+) liver tumor-initiating cells drive self-renewal and tumor initiation through STAT3-mediated NANOG regulation.
abstract: Tumor-initiating cells (T-ICs) are a subpopulation of chemoresistant tumor cells that have been shown to cause tumor recurrence upon chemotherapy. Identification of T-ICs and their related pathways are therefore priorities for the development of new therapeutic paradigms. We established chemoresistant hepatocellular carcinoma (HCC) xenograft tumors in immunocompromised mice in which an enriched T-IC population was capable of tumor initiation and self-renewal. With this model, we found CD24 to be upregulated in residual chemoresistant tumors when compared with bulk tumor upon cisplatin treatment. CD24(+) HCC cells were found to be critical for the maintenance, self-renewal, differentiation, and metastasis of tumors and to significantly impact patients' clinical outcome. With a lentiviral-based knockdown approach, CD24 was found to be a functional liver T-IC marker that drives T-IC genesis through STAT3-mediated NANOG regulation. Our findings point to a CD24 cascade in liver T-ICs that may provide an attractive therapeutic target for HCC patients.
authors: State Key Laboratory for Liver Research, The University of Hong Kong, Pokfulam.
authors: Terence Kin Wah
authors: TK
authors: Lee
authors: Antonia
authors: A
authors: Castilho
authors: Vincent Chi Ho
authors: VC
authors: Cheung
authors: Kwan Ho
authors: KH
authors: Tang
authors: Stephanie
authors: S
authors: Ma
authors: Irene Oi Lin
authors: IO
authors: Ng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D051927:CD24 Antigen / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008875:Middle Aged; D000071317:Nanog Homeobox Protein; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D051927:CD24 Antigen; D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human