ABCC4 suppresses glioblastoma progression and recurrence by restraining cGMP-PKG signalling

Jung-Ying Chiang1,2, Sung-Tai Wei3,4, Huan-Jui Chang1,5

  • 1Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.

British Journal of Cancer
|February 12, 2024
PubMed
Abstract

Insights

ATP-binding cassette sub-family C member 4 (ABCC4) acts as a tumor suppressor in glioblastoma by inhibiting cyclic guanosine monophosphate (cGMP) signaling. Aspirin hydrogels restore ABCC4, impeding glioblastoma progression and recurrence.

Area of Science:

  • Neuro-oncology
  • Cancer biology
  • Molecular signaling

Background:

  • Cyclic nucleotides regulate glioblastoma (GBM) cell signaling.
  • Mechanisms controlling cyclic nucleotides in GBM progression remain unclear.

Purpose of the Study:

  • Identify the primary regulator of cyclic nucleotides in recurrent GBM.
  • Investigate the functional role of cyclic nucleotide signaling in GBM.
  • Evaluate therapeutic strategies targeting cyclic nucleotide pathways.

Main Methods:

  • In silico, mRNA, and protein analyses.
  • Lentiviral and pharmacological manipulations in glioma cell lines.
  • Orthotopic xenograft mouse models with aspirin hydrogels.

Main Results:

  • Reduced ATP-binding cassette sub-family C member 4 (ABCC4) expression elevates intracellular cyclic guanosine monophosphate (cGMP), promoting GBM recurrence.
  • ABCC4 loss-of-function activates cGMP-protein kinase G (PKG) signaling, increasing malignancy.
  • Aspirin hydrogels upregulate ABCC4, inhibiting tumor progression and enhancing standard therapies.

Conclusions:

  • ABCC4 functions as a tumor suppressor in GBM by inhibiting the cGMP-PKG pathway.
  • Targeting ABCC4 with aspirin hydrogels represents a promising therapeutic strategy for GBM.

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