PGD2/PTGDR2 Signaling Affects the Stemness of Gastric Cancer Stem Cells by Regulating Autophagy

Feifan Wang1,2, Hengjin Tian2, Peiyao Gao3

  • 1Department of Blood Transfusion, The First Affiliated Hospital of Naval Medical University, Shanghai, China.

Abstract

Insights

Prostaglandin D2 (PGD2) inhibits gastric cancer stem cell (GCSC) stemness and promotes autophagy. PGD2/PTGDR2 signaling regulates GCSC stemness and autophagy, offering potential therapeutic targets.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Signaling

Background:

  • Prostaglandin D2 (PGD2) is known to inhibit gastric cancer (GC) development.
  • The specific role of PGD2 in the autophagic death of GC stem cells (GCSCs) is not well understood.
  • Investigating PGD2's mechanisms in regulating GCSC stemness is crucial.

Purpose of the Study:

  • To elucidate the mechanisms by which PGD2 influences the stemness of GCSCs.
  • To determine the relationship between PGD2 signaling and autophagic death in GCSCs.

Main Methods:

  • HGC27-derived GCSCs were utilized, with knockdown of PGD2 receptor 2 (PTGDR2).
  • Assessed cell stemness via sphere-forming capacity.
  • Evaluated autophagic activity using transmission electron microscopy and western blot analyses.

Main Results:

  • PGD2 suppressed GCSC stemness and induced autophagy; PTGDR2 downregulation reversed these effects.
  • PGD2 inhibited stemness-associated proteins CD44 and OCT4.
  • Autophagy modulators 3-MA and RAPA influenced stemness markers, indicating a regulatory role.

Conclusions:

  • PGD2/PTGDR2 signaling significantly impacts stemness and autophagy in GCSCs.
  • PGD2/PTGDR2 signaling appears to regulate GCSC stemness through modulation of autophagy.
  • These findings suggest PGD2/PTGDR2 signaling as a potential therapeutic target in gastric cancer.

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