Loss of NDUFS1 promotes gastric cancer progression by activating the mitochondrial ROS-HIF1α-FBLN5 signaling pathway

Tao Chen1, Dongbao Li1, Yunliang Wang1

  • 1Department of General Surgery, the First Affiliated Hospital of Soochow University, 215006, Suzhou, China.

PubMed
Abstract

Insights

NDUFS1 downregulation promotes gastric cancer (GC) progression. This occurs through activation of the mitochondrial reactive oxygen species (mROS)-hypoxia-inducible factor 1α (HIF1α)-fibulin 5 (FBLN5) pathway, driving cancer cell growth and metastasis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • NDUFS1's role in human cancers is recognized, but its specific impact on gastric cancer (GC) remains unclear.
  • Gastric cancer (GC) is a significant global health concern with complex underlying molecular mechanisms.

Purpose of the Study:

  • To investigate the role and mechanism of NDUFS1 in gastric cancer (GC) progression.
  • To elucidate the signaling pathway involved in NDUFS1-mediated GC development.

Main Methods:

  • Western blot, immunohistochemistry, and bioinformatics analysis to assess NDUFS1 expression in GC.
  • In vitro (CCK-8, colony formation, Transwell assays) and in vivo (mouse xenograft) experiments to evaluate NDUFS1's functional impact.
  • Confocal microscopy to observe NDUFS1 localization and mitochondrial reactive oxygen species (mROS) levels.

Main Results:

  • NDUFS1 expression was significantly downregulated in GC tissues and cell lines.
  • NDUFS1 overexpression suppressed GC cell proliferation, migration, invasion, and tumor growth in vivo.
  • NDUFS1 reduction activated the mROS-hypoxia-inducible factor 1α (HIF1α) pathway, leading to increased fibulin 5 (FBLN5) expression.

Conclusions:

  • NDUFS1 downregulation is a key driver of gastric cancer (GC) progression.
  • The mROS-HIF1α-FBLN5 signaling pathway is critically involved in NDUFS1-mediated GC development.
  • Targeting NDUFS1 or this pathway may offer therapeutic strategies for gastric cancer.

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