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The HHEX-ABI2/SLC17A9 axis induces cancer stem cell-like properties and tumorigenesis in HCC

J Transl Med. 2024 Jun 6;22(1):537. doi: 10.1186/s12967-024-05324-2.

Abstract

Accumulating evidence indicated that HHEX participated in the initiation and development of several cancers, but the potential roles and mechanisms of HHEX in hepatocellular carcinoma (HCC) were largely unclear. Cancer stem cells (CSCs) are responsible for cancer progression owing to their stemness characteristics. We reported that HHEX was a novel CSCs target for HCC. We found that HHEX was overexpressed in HCC tissues and high expression of HHEX was associated with poor survival. Subsequently, we found that HHEX promoted HCC cell proliferation, migration, and invasion. Moreover, bioinformatics analysis and experiments verified that HHEX promoted stem cell-like properties in HCC. Mechanistically, ABI2 serving as a co-activator of transcriptional factor HHEX upregulated SLC17A9 to promote HCC cancer stem cell-like properties and tumorigenesis. Collectively, the HHEX-mediated ABI2/SLC17A9 axis contributes to HCC growth and metastasis by maintaining the CSC population, suggesting that HHEX serves as a promising therapeutic target for HCC treatment.

Keywords: Cancer stem cells; Hepatocellular carcinoma; Molecular targeting; Signal transduction pathways; Translational oncology.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Carcinogenesis* / pathology
  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / metabolism
  • Carcinoma, Hepatocellular* / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Homeodomain Proteins* / metabolism
  • Humans
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / metabolism
  • Liver Neoplasms* / pathology
  • Mice, Nude
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplastic Stem Cells* / metabolism
  • Neoplastic Stem Cells* / pathology
  • Nucleotide Transport Proteins* / metabolism
  • Signal Transduction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • ABI2 protein, human
  • Adaptor Proteins, Signal Transducing
  • HHEX protein, human
  • Homeodomain Proteins
  • Nucleotide Transport Proteins
  • Slc17a9 protein, human
  • Transcription Factors