CD24 + Liver Tumor-Initiating Cells Drive Self-Renewal and Tumor Initiation through STAT3-Mediated NANOG Regulation

Kin Wah Lee, Antonia Castilho, Vincent Chi Ho Cheung, Kwan Ho Tang, Stephanie Ma, Irene Oi Lin Ng

Research output: Journal article publicationJournal articleAcademic researchpeer-review

413 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)50-63
Number of pages14
JournalCell Stem Cell
Volume9
Issue number1
DOIs
Publication statusPublished - 8 Jul 2011
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine
  • Genetics

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