CD24 regulates sorafenib resistance via activating autophagy in hepatocellular carcinoma

Shuai Lu1,2,3, Yao Yao1,4, Guolong Xu1,2,3

  • 1Department of Immunology, Nanjing Medical University, Nanjing, 211166, China.

Insights

CD24 overexpression drives sorafenib resistance in hepatocellular carcinoma (HCC) by activating autophagy. Targeting CD24 and autophagy offers a promising strategy for overcoming drug resistance in HCC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Hepatocellular carcinoma (HCC) is a prevalent global cancer.
  • Sorafenib is a key treatment for advanced HCC, but drug resistance limits its efficacy.
  • Mechanisms underlying sorafenib resistance in HCC are not fully understood.

Purpose of the Study:

  • To investigate the role of CD24 in sorafenib resistance in HCC.
  • To elucidate the molecular mechanisms linking CD24 to sorafenib resistance.
  • To explore potential therapeutic strategies targeting CD24 and autophagy.

Main Methods:

  • Analysis of CD24 expression in HCC tumor tissues and cell lines.
  • Assessment of sorafenib sensitivity in HCC cell lines with varying CD24 levels.
  • Investigation of autophagy activation and its modulation by CD24.
  • Examination of the mTOR/AKT pathway and PP2A protein in relation to CD24 and autophagy.

Main Results:

  • CD24 is overexpressed in HCC tissues and sorafenib-resistant cell lines, correlating positively with resistance.
  • CD24 depletion enhances sorafenib sensitivity in resistant HCC cells.
  • CD24-mediated resistance involves autophagy activation, which can be inhibited pharmacologically or genetically.
  • CD24 overexpression increases PP2A, deactivates mTOR/AKT, and subsequently enhances autophagy.

Conclusions:

  • CD24 plays a critical role in regulating sorafenib resistance in HCC through autophagy activation.
  • This study establishes a novel link between CD24, autophagy, and sorafenib resistance.
  • Combined targeting of CD24 and autophagy modulation presents a promising therapeutic approach for HCC treatment.

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