FGF2/FGFR1 regulates autophagy in FGFR1-amplified non-small cell lung cancer cells

Hong Yuan1,2, Zi-Ming Li1, Jiaxiang Shao2

  • 1Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, China.

Abstract

Insights

Fibroblast growth factor receptor 1 (FGFR1) activation suppresses autophagy in lung cancer. Inhibiting FGFR1 or the ERK/MAPK pathway induces autophagy, enhancing cell death when combined with autophagy inhibition.

Area of Science:

  • Cellular Biology
  • Cancer Research
  • Molecular Oncology

Background:

  • Autophagy, a cellular degradation process, has a complex role in cancer development.
  • Fibroblast growth factor receptor 1 (FGFR1) amplification is common in lung squamous cell carcinoma (SQCC).
  • The specific role of fibroblast growth factor 2 (FGF2)/FGFR1 in regulating autophagy remains unclear.

Purpose of the Study:

  • To investigate the role of FGF2/FGFR1 signaling in autophagy regulation within lung cancer.
  • To determine the therapeutic potential of targeting FGFR1 and autophagy concurrently in non-small cell lung cancer (NSCLC).

Main Methods:

  • Autophagic activity assessed via LC3 immunoblotting, GFP-LC3 puncta, and monodansylcadaverine (MDC) staining.
  • Cell viability and apoptosis assays evaluated the impact of autophagy inhibition.
  • Pharmacological (AZD4547) and genetic (shRNA) inhibition of FGFR1 were employed.

Main Results:

  • FGFR1 activation was found to suppress autophagy.
  • Inhibition of FGFR1 (pharmacologically or genetically) induced autophagy in NSCLC cells.
  • Autophagy induction by FGFR1 inhibition was mediated by the ERK/MAPK pathway, not AKT, and involved beclin-1 upregulation.
  • Combined inhibition of FGFR1 and autophagy enhanced cancer cell apoptosis.

Conclusions:

  • Simultaneous inhibition of FGFR1 and autophagy presents a promising therapeutic strategy for enhancing cancer cell death.
  • Further in vivo studies are warranted to validate these findings.

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