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Updated: May 17, 2025

A Chromatin Immunoprecipitation Assay to Identify Novel NFAT2 Target Genes in Chronic Lymphocytic Leukemia
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NFAT2 promotes sorafenib resistance in hepatocellular carcinoma cells by modulating calcium ion signalling

Jian Wang1, Yi Bai2, Xian-Yi Liu1

  • 1Department of Comprehensive Surgery, Tianjin First Central Hospital, Tianjin, China.

Archives of Biochemistry and Biophysics
|April 27, 2025
PubMed

Insights

Nuclear factor activated T cells 2 (NFAT2) promotes sorafenib resistance in hepatocellular carcinoma (HCC) by altering calcium signaling. Targeting NFAT2 offers a new therapeutic strategy for overcoming drug resistance in HCC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Hepatocellular carcinoma (HCC) treatment is hindered by drug resistance, particularly to sorafenib.
  • Understanding mechanisms of sorafenib resistance is crucial for developing effective therapies.

Purpose of the Study:

  • To investigate the role of nuclear factor activated T cells 2 (NFAT2) in sorafenib resistance in HCC cells.
  • To elucidate the underlying molecular mechanisms by which NFAT2 influences sorafenib resistance.

Main Methods:

  • Construction of sorafenib-resistant HCC cell lines with NFAT2 overexpression and knockdown.
  • Assessment of intracellular calcium ion concentration, organelle damage, cell migration, invasion, proliferation, and apoptosis.
  • Analysis of protein expression via Western blot and evaluation of tumorigenesis in a mouse model.

Main Results:

  • NFAT2 was upregulated in sorafenib-resistant HCC cells.
  • NFAT2 overexpression reduced intracellular calcium influx and related protein expression, inhibited apoptosis, and enhanced cell proliferation, migration, and invasion.
  • NFAT2 knockdown decreased tumorigenesis in vivo.

Conclusions:

  • NFAT2 plays a significant role in promoting sorafenib resistance in HCC by modulating intracellular calcium signaling pathways.
  • NFAT2 represents a potential therapeutic target for overcoming sorafenib resistance in hepatocellular carcinoma.
Keywords:
Calcium ionDrug resistanceHepatocellular carcinomaNFAT2Sorafenib

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