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Updated: Sep 1, 2025

Modeling Oral-Esophageal Squamous Cell Carcinoma in 3D Organoids
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NADPH Oxidase 2 Has a Crucial Role in Cell Cycle Progression of Esophageal Squamous Cell Carcinoma

Hiroki Shimizu1, Keita Katsurahara1, Hiroyuki Inoue1

  • 1Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Annals of Surgical Oncology
|August 16, 2022
PubMed
Abstract

Insights

NADPH oxidase 2 (NOX2) expression drives esophageal squamous cell carcinoma (ESCC) tumorigenesis and progression. Targeting NOX2 may offer a new therapeutic strategy for ESCC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • NADPH oxidases (NOXs) generate reactive oxygen species and are implicated in cancer progression.
  • The specific role of NOX2 in esophageal squamous cell carcinoma (ESCC) is not well understood.

Purpose of the Study:

  • To investigate the pathophysiologic role and prognostic significance of NOX2 in ESCC.
  • To explore the molecular mechanisms underlying NOX2's function in ESCC.

Main Methods:

  • Utilized human ESCC cell lines (TE5, KYSE170) for transfection experiments.
  • Performed mRNA microarray analysis to examine gene expression profiles.
  • Conducted immunohistochemistry on 130 ESCC tumor samples to assess NOX2 expression and patient prognosis.

Main Results:

  • NOX2 depletion inhibited ESCC cell proliferation, induced G0/G1 cell cycle arrest, and promoted apoptosis.
  • NOX2 gene expression correlated with the cell cycle regulation pathway involving BTG2 family genes (BTG2, CCNE2, E2F1, CDK2).
  • High NOX2 protein expression in tumors was linked to deeper invasion and served as an independent prognostic factor for 5-year overall survival.

Conclusions:

  • NOX2 expression influences ESCC tumorigenesis, cell cycle progression via the BTG2 pathway, and patient prognosis.
  • NOX2 represents a potential novel biomarker and therapeutic target for esophageal squamous cell carcinoma.

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