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Reduced IQGAP2 promotes esophageal squamous cell carcinoma by regulating MEK/ERK MAPK pathway

Liangcheng Zhao1

  • 1Department of Gastroenterology, The Fifth People's Hospital of Wujiang District, Suzhou, Jiangsu, China.

Frontiers in Genetics
|August 24, 2026
PubMed
Abstract

Insights

IQ motif-containing GTPase activating protein 2 (IQGAP2) is decreased in esophageal squamous cell carcinoma (ESCC). Lower IQGAP2 levels promote ESCC cell proliferation by activating the MEK/ERK MAPK pathway, suggesting IQGAP2 as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • IQ motif-containing GTPase activating protein 2 (IQGAP2) functions as a tumor suppressor in multiple cancer types.
  • The specific role of IQGAP2 in esophageal squamous cell carcinoma (ESCC) pathogenesis is not well-defined.

Purpose of the Study:

  • To investigate the expression levels of IQGAP2 in ESCC tissues.
  • To elucidate the functional role of IQGAP2 in ESCC cell proliferation.
  • To explore the underlying molecular mechanisms, particularly the MEK/ERK MAPK pathway.

Main Methods:

  • IQGAP2 expression analysis in 236 ESCC patient tumor tissues via RNA sequencing and qPCR.
  • Establishment of ESCC cell lines with IQGAP2 overexpression and knockdown using lentiviral methods.
  • Assessment of cell proliferation using CCK-8 assays and MEK/ERK MAPK pathway activation via Western blotting.

Main Results:

  • IQGAP2 expression was significantly downregulated in ESCC tumor samples compared to normal tissues.
  • IQGAP2 overexpression inhibited ESCC cell proliferation, while IQGAP2 knockdown promoted it.
  • Reduced IQGAP2 expression was found to enhance ESCC cell proliferation through activation of the MEK/ERK MAPK signaling pathway.

Conclusions:

  • IQGAP2 acts as a tumor suppressor in ESCC.
  • The downregulation of IQGAP2 contributes to ESCC progression via the MEK/ERK MAPK pathway.
  • IQGAP2 represents a potential therapeutic target for ESCC treatment.

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