DNAJC24 is a potential therapeutic target in hepatocellular carcinoma through affecting ammonia metabolism

Guangtao Li1,2,3, Yuchao He1,3, Hui Liu1,3

  • 1Department of Tumor Cell Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.

Insights

High expression of DNAJC24, a heat shock protein, is linked to shorter survival in hepatocellular carcinoma (HCC) patients. Targeting DNAJC24 may offer a new therapeutic strategy for HCC by inhibiting cancer progression.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Biology

Background:

  • Heat shock proteins (HSPs) are crucial for cellular stress response and survival.
  • In malignant tumors, HSPs can aid tumor cells in coping with stress and treatment, potentially promoting cancer progression.

Purpose of the Study:

  • To investigate the role of DNAJC24, a heat shock protein, in hepatocellular carcinoma (HCC).
  • To determine if DNAJC24 expression correlates with patient survival and HCC progression.
  • To explore DNAJC24 as a potential therapeutic target for HCC.

Main Methods:

  • Immunohistochemical staining of 167 paired HCC and paraneoplastic tissues.
  • Analysis of public database data.
  • In vitro experiments involving stimuli like hypoxia, starvation, and heat.
  • Investigation of DNAJC24's effect on HCC cell proliferation, motility, autophagy, and ammonia metabolism.

Main Results:

  • High DNAJC24 expression was correlated with shortened survival in HCC patients.
  • Hypoxia, starvation, and heat upregulated DNAJC24 expression in HCC cells via HSF2 transcriptional regulation.
  • Elevated DNAJC24 promoted HCC cell proliferation and motility.
  • Targeting DNAJC24 inhibited HCC cell proliferation and autophagy by interfering with ammonia metabolism, thus hindering malignant progression.

Conclusions:

  • DNAJC24 is a significant factor in HCC progression and patient survival.
  • DNAJC24 upregulation is mediated by cellular stress through HSF2.
  • DNAJC24 represents a promising novel therapeutic target for hepatocellular carcinoma treatment.