Related Experiment Video

Updated: Jan 28, 2026

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
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Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays

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Glycerol kinase 5 confers gefitinib resistance through SREBP1/SCD1 signaling pathway

Jian Zhou1, Guimei Qu2, Ge Zhang1

  • 1Department of Pulmonary Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China.

Journal of Experimental & Clinical Cancer Research : CR
|February 23, 2019
PubMed
Abstract

Insights

Glycerol kinase 5 (GK5) drives gefitinib resistance in non-small cell lung cancer (NSCLC) by blocking apoptosis and cell cycle arrest. Targeting GK5 may overcome resistance to EGFR tyrosine kinase inhibitors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Drug resistance is a significant challenge in cancer chemotherapy.
  • Glycerol kinase 5 (GK5) is investigated for its role in mediating gefitinib resistance in non-small cell lung cancer (NSCLC).

Purpose of the Study:

  • To investigate the role of GK5 in gefitinib resistance in NSCLC.
  • To explore GK5 as a potential therapeutic target for overcoming resistance to EGFR tyrosine kinase inhibitors.

Main Methods:

  • Exosomal GK5 mRNA detection using a tethered cationic lipoplex nanoparticle (TCLN) biochip.
  • Real-time PCR and Western blot to assess GK5 expression.
  • Cell proliferation, cell cycle, and mitochondrial membrane potential assays (CCK-8, EdU, flow cytometry, JC-1).

Main Results:

  • Elevated exosomal GK5 mRNA in plasma of gefitinib-resistant NSCLC patients.
  • Upregulated GK5 mRNA and protein in gefitinib-resistant cell lines (PC9R, H1975) compared to sensitive cells (PC9).
  • GK5 silencing in PC9R cells induced mitochondrial damage, caspase activation, cell cycle arrest, and apoptosis via the SREBP1/SCD1 pathway.

Conclusions:

  • GK5 confers gefitinib resistance in lung cancer by inhibiting apoptosis and cell cycle arrest.
  • GK5 represents a novel therapeutic target for NSCLC resistant to EGFR tyrosine kinase inhibitors.
Keywords:
GefitinibGlycerol kinase 5Non-small cell lung cancerStearoyl-CoA desaturase-1

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