Related Experiment Video

Updated: Feb 11, 2026

A "Patient-Like" Orthotopic Syngeneic Mouse Model of Hepatocellular Carcinoma Metastasis
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DLGAP5 regulates malignancy and lenvatinib sensitivity of hepatocellular carcinoma through AKT/mTOR/NF-κB pathway

Benyi He1,2, Min Deng3, Renguo Guan4

  • 1Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China.

European Journal of Medical Research
|February 10, 2026
PubMed
Abstract

Insights

Discs Large Homolog Associated Protein 5 (DLGAP5) promotes hepatocellular carcinoma (HCC) malignancy and reduces lenvatinib sensitivity. Downregulating DLGAP5 inhibits tumor growth and improves treatment response in HCC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Lenvatinib is a first-line treatment for advanced hepatocellular carcinoma (HCC).
  • Drug resistance to lenvatinib presents a significant challenge in improving patient outcomes.
  • Discs Large Homolog Associated Protein 5 (DLGAP5), a cell-cycle-regulated protein, is linked to poor cancer prognosis, but its role in lenvatinib sensitivity in HCC is unknown.

Purpose of the Study:

  • To investigate the biological roles and mechanisms of DLGAP5 in lenvatinib sensitivity in HCC.
  • To explore DLGAP5 as a potential biomarker for prognosis and lenvatinib treatment efficacy in HCC.

Main Methods:

  • Analysis of DLGAP5 expression in public databases and a cohort of 60 HCC patients.
  • In vitro and in vivo experiments assessing cell growth, metastasis, and apoptosis following DLGAP5 modulation.
  • RNA-sequencing to analyze differentially expressed genes in DLGAP5-knockdown HCC cells.

Main Results:

  • DLGAP5 is upregulated in HCC tissues, particularly in metastatic lesions, and correlates with poor prognosis and reduced lenvatinib response.
  • Downregulation of DLGAP5 inhibited HCC malignancy and enhanced sensitivity to lenvatinib in vitro and in vivo.
  • DLGAP5 appears to regulate the AKT/mTOR/NF-κB signaling pathway.

Conclusions:

  • DLGAP5 promotes HCC malignancy and diminishes lenvatinib sensitivity by positively regulating the AKT/mTOR/NF-κB pathway.
  • DLGAP5 serves as a potential biomarker for clinical prognosis and predicting lenvatinib treatment outcomes in HCC.
Keywords:
DLGAP5Hepatocellular carcinomaLenvatinibNF-κBPrognosis

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