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GKN2 promotes oxidative stress-induced gastric cancer cell apoptosis via the Hsc70 pathway

Ziqiang Zhang1, Hongyuan Xue1, Yuanqiang Dong1

  • 1Departments of General Surgery, Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai, 200040, People's Republic of China.

Journal of Experimental & Clinical Cancer Research : CR
|August 7, 2019
PubMed
Abstract

Insights

Gastric cancer protein GKN2, when overexpressed, enhances apoptosis and inhibits tumor growth. GKN2 may serve as a prognostic biomarker for oxaliplatin treatment in gastric cancer patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • GKN2 is a secretory protein with decreased levels in gastric cancer.
  • Its role in gastric cancer progression and treatment response requires further elucidation.

Purpose of the Study:

  • To investigate the expression, function, and mechanism of GKN2 in gastric cancer.
  • To assess GKN2's potential as a prognostic biomarker.

Main Methods:

  • In vitro and in vivo molecular biology assays were employed.
  • Clinical specimens were analyzed to correlate GKN2 expression with patient prognosis.
  • Mechanisms involving signaling pathways (NF-κB, JNK) and protein interactions (GKN2-Hsc70) were studied.

Main Results:

  • GKN2 overexpression induced apoptosis and growth arrest in gastric cancer cells.
  • GKN2 modulated reactive oxygen species-induced mitochondrial dysfunction and inhibited NF-κB/activated JNK signaling.
  • GKN2 inhibited xenograft tumor growth and was a significant prognostic factor for oxaliplatin-treated patients.

Conclusions:

  • GKN2 enhances gastric cancer cell sensitivity to ROS-increasing drugs.
  • GKN2's interaction with Hsc70 is crucial for its effects.
  • GKN2 overexpression can identify patients likely to benefit from oxaliplatin therapy, serving as a prognostic biomarker.
Keywords:
ApoptosisGKN2Gastric cancerOxidative stress

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