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Integrin αV Inhibition by GMI, a Ganoderma Microsporum Immunomodulatory Protein, Abolish Stemness and Migration in

Yu-Ting Kang1,2, Hui-Yi Chang1, Ya-Chu Hsieh1

  • 1Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.

Environmental Toxicology
|August 17, 2024
PubMed

Insights

Ganoderma microsporum protein GMI inhibits lung cancer stemness and migration. It targets the integrin alphaV signaling pathway in EGFR-mutated, osimertinib-resistant cells, offering a novel therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Integrins mediate cancer cell proliferation and metastasis.
  • Ganoderma microsporum immunomodulatory protein (GMI) exhibits anticancer properties.
  • Osimertinib resistance in EGFR-mutated lung cancer presents a therapeutic challenge.

Purpose of the Study:

  • Investigate GMI's role in integrin signaling in EGFR-mutated, osimertinib-resistant lung cancer.
  • Determine GMI's effect on integrin expression and cancer stemness.
  • Elucidate GMI's mechanism in overcoming osimertinib resistance.

Main Methods:

  • Utilized H1975 lung cancer cells and established osimertinib-resistant H1975/TR cells.
  • Employed liquid chromatography-mass spectrometry and western blot assays.
  • Assessed cell viability, migration, tumor spheroid growth, and stemness markers.

Main Results:

  • GMI inhibited integrin expression, cell viability, migration, and xenograft tumor growth in H1975 cells.
  • H1975/TR cells showed higher Integrin αV and stemness marker expression.
  • GMI suppressed H1975/TR cell viability, spheroid growth, and integrin αV/β1 expression.
  • GMI blocked integrin αV signaling, reducing stemness markers and tumor sphere formation.

Conclusions:

  • GMI constrains cancer stem cells and migration in EGFR-mutated, osimertinib-resistant lung cancer.
  • GMI acts by abolishing the integrin αV-related signaling pathway.
  • This study reveals a novel function of GMI against resistant lung cancer phenotypes.
Keywords:
GMIcancer stem cellsintegrinlung cancermigrationosimertinib‐resistance

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