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CLIC4 inhibits the progression of non-small cell lung cancer by suppressing the MAPK pathway

Pengxiang Gao1,2, Wanjun Lu1, Xinyu Tan3

  • 1Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang City, 330006, Jiangxi Province, China.

Scientific Reports
|July 21, 2026
PubMed

Insights

Intracellular chloride channel protein 4 (CLIC4) is downregulated in non-small cell lung cancer (NSCLC). CLIC4 suppresses tumor progression by inhibiting MAPK signaling, suggesting its potential as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Intracellular chloride channel protein 4 (CLIC4) plays roles in cellular functions and is linked to apoptosis.
  • The expression and function of CLIC4 in various cancers, including non-small cell lung cancer (NSCLC), are not well-defined.
  • CLIC4 is regulated by signaling molecules like TGF-β, P53, Myc, and TNFα.

Purpose of the Study:

  • To investigate the expression patterns and functional significance of CLIC4 in non-small cell lung cancer (NSCLC).
  • To explore the potential of CLIC4 as a diagnostic or therapeutic target in NSCLC.

Main Methods:

  • Bioinformatics analysis to assess CLIC4 expression in NSCLC.
  • Experimental validation using cell lines with CLIC4 overexpression or knockdown.
  • RNA sequencing and western blotting to analyze signaling pathway modulation.

Main Results:

  • CLIC4 expression was found to be reduced in NSCLC.
  • Overexpression of CLIC4 inhibited NSCLC cell proliferation, migration, and invasion.
  • CLIC4 was identified to suppress MAPK-related signaling pathways.

Conclusions:

  • CLIC4 acts as a tumor suppressor in NSCLC by downregulating MAPK signaling.
  • CLIC4 represents a potential novel diagnostic and therapeutic target for NSCLC.
Keywords:
AKTCLIC4MAPKNSCLC

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