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APOE modulates ferroptosis to drive macrophage polarization toward the M2 type and enhance PTC migration and invasion

Ziwen Li1, Min Li2, Sinuo Sun1

  • 1Department of Morphology Laboratory, Zhangjiakou Key Laboratory, Hebei North University, Zhangjiakou 075000, China.

Immunobiology
|April 17, 2025
PubMed
Abstract

Insights

Apolipoprotein E (APOE) promotes papillary thyroid cancer (PTC) invasion and migration by inhibiting ferroptosis and driving M2 macrophage polarization via the PI3K/AKT1 pathway.

Area of Science:

  • Oncology
  • Cell Biology
  • Immunology

Background:

  • Apolipoprotein E (APOE) is linked to papillary thyroid carcinoma (PTC) cell invasion, migration, and M2 macrophage polarization.
  • Ferroptosis is implicated in tumor development and treatment resistance, with APOE involvement noted.
  • The precise role of APOE in PTC progression via ferroptosis modulation requires elucidation.

Purpose of the Study:

  • To investigate the ferroptosis-related mechanisms by which APOE influences PTC cell invasion, migration, and macrophage polarization.
  • To explore the PI3K/AKT1 pathway's role in APOE-mediated ferroptosis regulation in PTC.
  • To validate the interplay between ferroptosis, macrophages, and PTC progression.

Main Methods:

  • Assessed expression of APOE, xCT, GPX4, FTH1, and Fe2+ in PTC tissues via immunohistochemistry, Prussian blue staining, and western blot.
  • Utilized immunofluorescence, electron microscopy, RT-qPCR, western blot, and colorimetric assays to examine APOE's effects on ferroptosis.
  • Conducted in vivo experiments, co-culture systems, wound healing, and Transwell assays to validate findings.

Main Results:

  • PTC tissues showed lower Fe2+ accumulation but higher expression of APOE, xCT, GPX4, and FTH1 compared to normal tissues.
  • APOE was found to inhibit ferroptosis in PTC cells, potentially via the PI3K/AKT1 pathway and modulation of Fe2+ accumulation.
  • APOE enhanced PTC cell invasion and migration by promoting M2 macrophage polarization through ferroptosis inhibition.

Conclusions:

  • APOE regulates ferroptosis via the PI3K/AKT1 pathway in PTC.
  • APOE-driven ferroptosis inhibition promotes M2 macrophage polarization.
  • This mechanism contributes to enhanced invasion and migration of PTC cells.
Keywords:
APOEFe(2+)FerroptosisM2 macrophagesPI3K/AKT1

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