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2000
Volume 29, Issue 1
  • ISSN: 1386-2073
  • E-ISSN: 1875-5402

Abstract

Background

Prostaglandin D2 (PGD2) can inhibit the development of gastric cancer (GC); however, its role in the autophagic death of GC stem cells (GCSCs) remains elusive. Therefore, this study aims to evaluate the mechanisms by which PGD2 regulates the stemness in GCSCs.

Methods

In this study, HGC27-derived GCSCs were employed to knock down PGD2 receptor 2 (PTGDR2). Subsequently, cell stemness and autophagic activity in these GCSCs were assessed sphere-forming capacity, transmission electron microscopy, and western blot analyses.

Results

The results revealed that PGD2 suppressed the stemness of GCSCs and induced GCSCs autophagy, whereas the downregulation of PTGDR2 had the opposite effect. Furthermore, PGD2 was also found to inhibit the expression of stemness-associated proteins CD44 and OCT4, which were blocked by 3-MA and enhanced by RAPA. Moreover, the shPTGDR2 + PGD2 group indicated higher stemness than the PGD2 group, with 3-MA enhancing this effect and RAPA reducing this change.

Conclusion

In summary, this study indicated that PGD2/PTGDR2 signaling affects stemness and autophagy in GCSCs. The results suggest that PGD2/PTGDR2 signaling may affect the stemness of GCSCs by regulating autophagy.

© 2026 Bentham Science Publishers
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2026-01-01
2026-02-17

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References

  1. SungH. FerlayJ. SiegelR.L. LaversanneM. SoerjomataramI. JemalA. BrayF. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J. Clin.202171320924910.3322/caac.21660 33538338
     [Google Scholar]
  2. LiZ. ShanF. YingX. ZhangY. EJ.Y. WangY. RenH. SuX. JiJ. Assessment of laparoscopic distal gastrectomy after neoadjuvant chemotherapy for locally advanced gastric cancer.JAMA Surg.2019154121093110110.1001/jamasurg.2019.3473 31553463
     [Google Scholar]
  3. LuoS. LiY. MaR. LiuJ. XuP. ZhangH. TangK. MaJ. LiuN. ZhangY. SunY. JiT. LiangX. YinX. LiuY. TongW. NiuY. WangN. WangX. HuangB. Downregulation of PCK2 remodels tricarboxylic acid cycle in tumor-repopulating cells of melanoma.Oncogene201736253609361710.1038/onc.2016.520 28166201
     [Google Scholar]
  4. YangY. MengW.J. WangZ.Q. The origin of gastric cancer stem cells and their effects on gastric cancer: Novel therapeutic targets for gastric cancer.Front. Oncol.20221296053910.3389/fonc.2022.960539 36185219
     [Google Scholar]
  5. YangL. ShiP. ZhaoG. XuJ. PengW. ZhangJ. ZhangG. WangX. DongZ. ChenF. CuiH. Targeting cancer stem cell pathways for cancer therapy.Signal Transduct. Target. Ther.202051810.1038/s41392‑020‑0110‑5 32296030
     [Google Scholar]
  6. BiddleA. MackenzieI.C. Cancer stem cells and EMT in carcinoma.Cancer Metastasis Rev.2012311-228529310.1007/s10555‑012‑9345‑0 22302111
     [Google Scholar]
  7. ZhangQ. WangF. HuangY. GaoP. WangN. TianH. ChenA. LiY. WangF. PGD2/PTGDR2 signal affects the viability, invasion, apoptosis, and stemness of gastric cancer stem cells and prevents the progression of gastric cancer.Comb. Chem. High Throughput Screen.202427693394610.2174/1386207326666230731103112 37526190
     [Google Scholar]
  8. CampbellJ.P. KarolakM.R. MaY. PerrienD.S. Masood-CampbellS.K. PennerN.L. MunozS.A. ZijlstraA. YangX. SterlingJ.A. ElefteriouF. Stimulation of host bone marrow stromal cells by sympathetic nerves promotes breast cancer bone metastasis in mice.PLoS Biol.2012107e100136310.1371/journal.pbio.1001363 22815651
     [Google Scholar]
  9. AkhavanO. GhaderiE. ShirazianS.A. RahighiR. Rolled graphene oxide foams as three-dimensional scaffolds for growth of neural fibers using electrical stimulation of stem cells.Carbon201697717710.1016/j.carbon.2015.06.079
     [Google Scholar]
  10. DayemA.A. ChoiH.Y. KimJ.H. ChoS.G. Role of oxidative stress in stem, cancer, and cancer stem cells.Cancers20102285988410.3390/cancers2020859 24281098
     [Google Scholar]
  11. TianH. GeK. WangL. GaoP. ChenA. WangF. GuoF. WangF. ZhangQ. Advances in PGD2/PTGDR2 signaling pathway in tumors: A review.Biomol. Biomed.20242451055106710.17305/bb.2024.10485 38704736
     [Google Scholar]
  12. ZhangB. BieQ. WuP. ZhangJ. YouB. ShiH. QianH. XuW. PGD2/PTGDR2 signaling restricts the self-renewal and tumorigenesis of gastric cancer.Stem Cells2018367990100310.1002/stem.2821 29604141
     [Google Scholar]
  13. ClarkeA.J. SimonA.K. Autophagy in the renewal, differentiation and homeostasis of immune cells.Nat. Rev. Immunol.201919317018310.1038/s41577‑018‑0095‑2 30531943
     [Google Scholar]
  14. DikicI. ElazarZ. Mechanism and medical implications of mammalian autophagy.Nat. Rev. Mol. Cell Biol.201819634936410.1038/s41580‑018‑0003‑4 29618831
     [Google Scholar]
  15. NakatogawaH. IchimuraY. OhsumiY. Atg8, a ubiquitin-like protein required for autophagosome formation, mediates membrane tethering and hemifusion.Cell2007130116517810.1016/j.cell.2007.05.021 17632063
     [Google Scholar]
  16. PadmanB.S. NguyenT.N. LazarouM. Autophagosome formation and cargo sequestration in the absence of LC3/GABARAPs.Autophagy201713477277410.1080/15548627.2017.1281492 28165849
     [Google Scholar]
  17. LiX. YangK.B. ChenW. MaiJ. WuX.Q. SunT. WuR.Y. JiaoL. LiD.D. JiJ. ZhangH.L. YuY. ChenY.H. FengG.K. DengR. LiJ.D. ZhuX.F. CUL3 (cullin 3)-mediated ubiquitination and degradation of BECN1 (beclin 1) inhibit autophagy and promote tumor progression.Autophagy202117124323434010.1080/15548627.2021.1912270 33977871
     [Google Scholar]
  18. AssaliA. AkhavanO. MottaghitalabF. AdeliM. DinarvandR. RazzazanS. ArefianE. SoleimaniM. AtyabiF. Cationic graphene oxide nanoplatform mediates miR-101 delivery to promote apoptosis by regulating autophagy and stress.Int. J. Nanomedicine2018135865588610.2147/IJN.S162647 30319254
     [Google Scholar]
  19. AssaliA. AkhavanO. AdeliM. RazzazanS. DinarvandR. ZanganehS. SoleimaniM. DinarvandM. AtyabiF. Multifunctional core-shell nanoplatforms (gold@graphene oxide) with mediated NIR thermal therapy to promote miRNA delivery.Nanomedicine20181461891190310.1016/j.nano.2018.05.016 29885900
     [Google Scholar]
  20. LiaoA. HuR. ZhaoQ. LiJ. LiY. YaoK. ZhangR. WangH. YangW. LiuZ. Autophagy induced by FTY720 promotes apoptosis in U266 cells.Eur. J. Pharm. Sci.201245560060510.1016/j.ejps.2011.12.014 22281442
     [Google Scholar]
  21. MaJ. CuiY. CaoT. XuH. ShiY. XiaJ. TaoY. WangZ.P. PDS5B regulates cell proliferation and motility via upregulation of Ptch2 in pancreatic cancer cells.Cancer Lett.2019460657410.1016/j.canlet.2019.06.014 31233836
     [Google Scholar]
  22. HanB. ZhengR. ZengH. WangS. SunK. ChenR. LiL. WeiW. HeJ. Cancer incidence and mortality in China, 2022.J. Natl. Cancer Cent.202441475310.1016/j.jncc.2024.01.006 39036382
     [Google Scholar]
  23. PrasadS. RamachandranS. GuptaN. KaushikI. SrivastavaS.K. Cancer cells stemness: A doorstep to targeted therapy.Biochim. Biophys. Acta Mol. Basis Dis.20201866416542410.1016/j.bbadis.2019.02.019 30818002
     [Google Scholar]
  24. HatfieldS. Ruohola-BakerH. microRNA and stem cell function.Cell Tissue Res.20083311576610.1007/s00441‑007‑0530‑3 17987317
     [Google Scholar]
  25. DelGiornoK.E. ChungC.Y. VavinskayaV. MaurerH.C. NovakS.W. LytleN.K. MaZ. GiraddiR.R. WangD. FangL. NaeemR.F. AndradeL.R. AliW.H. TsengH. TsuiC. GubbalaV.B. Ridinger-SaisonM. OhmotoM. EriksonG.A. O’ConnorC. ShokhirevM.N. HahN. UradeY. MatsumotoI. KaechS.M. SinghP.K. ManorU. OliveK.P. WahlG.M. Tuft cells inhibit pancreatic tumorigenesis in mice by producing Prostaglandin D2.Gastroenterology2020159518661881.e810.1053/j.gastro.2020.07.037 32717220
     [Google Scholar]
  26. AlvesM. Do AmaralN. MarchiF. SilvaF. Da CostaA. CarvalhoK. BaiocchiG. SoaresF. De BrotL. RochaR. Prostaglandin D2 expression is prognostic in high grade serous ovarian cancer.Oncol. Rep.20194142254226410.3892/or.2019.6984 30720106
     [Google Scholar]
  27. WuL. LinQ. MaZ. ChowdhuryF.A. MazumderM.H.H. DuW. Mesenchymal PGD2 activates an ILC2-Treg axis to promote proliferation of normal and malignant HSPCs.Leukemia202034113028304110.1038/s41375‑020‑0843‑8 32366935
     [Google Scholar]
  28. FuY. LiH. HaoX. The self-renewal signaling pathways utilized by gastric cancer stem cells.Tumour Biol.201739410.1177/1010428317697577 28378630
     [Google Scholar]
  29. ManiS.A. GuoW. LiaoM.J. EatonE.N. AyyananA. ZhouA.Y. BrooksM. ReinhardF. ZhangC.C. ShipitsinM. CampbellL.L. PolyakK. BriskenC. YangJ. WeinbergR.A. The epithelial-mesenchymal transition generates cells with properties of stem cells.Cell2008133470471510.1016/j.cell.2008.03.027 18485877
     [Google Scholar]
  30. WangB. ChenQ. CaoY. MaX. YinC. JiaY. ZangA. FanW. LGR5 is a gastric cancer stem cell marker associated with stemness and the EMT signature genes NANOG, NANOGP8, PRRX1, TWIST1, and BMI1.PLoS One20161112e016890410.1371/journal.pone.0168904 28033430
     [Google Scholar]
  31. MurataT. AritakeK. MatsumotoS. KamauchiS. NakagawaT. HoriM. MomotaniE. UradeY. OzakiH. Prostagladin D 2 is a mast cell-derived antiangiogenic factor in lung carcinoma.Proc. Natl. Acad. Sci. USA201110849198021980710.1073/pnas.1110011108 22106279
     [Google Scholar]
  32. BeilankouhiE.A.V. ValiloM. DastmalchiN. TeimourianS. SafaralizadehR. The function of autophagy in the initiation, and development of breast cancer.Curr. Med. Chem.202431202974299010.2174/0929867330666230503145319 37138421
     [Google Scholar]
  33. LemosG. FernandesC.M.A.S. SilvaF.H. CalmasiniF.B. The role of autophagy in prostate cancer and prostatic diseases: A new therapeutic strategy.Prostate Cancer Prostatic Dis.202427223023810.1038/s41391‑024‑00793‑4 38297152
     [Google Scholar]
  34. PhadwalK. WatsonA.S. SimonA.K. Tightrope act: Autophagy in stem cell renewal, differentiation, proliferation, and aging.Cell. Mol. Life Sci.20137018910310.1007/s00018‑012‑1032‑3 22669258
     [Google Scholar]
  35. VessoniA.T. MuotriA.R. OkamotoO.K. Autophagy in stem cell maintenance and differentiation.Stem Cells Dev.201221451352010.1089/scd.2011.0526 22066548
     [Google Scholar]
  36. LiL.Q. PanD. ZhangS.W. -Y-XieD. ZhengX.L. ChenH. Autophagy regulates chemoresistance of gastric cancer stem cells via the Notch signaling pathway.Eur. Rev. Med. Pharmacol. Sci.201822113402340710.26355/eurrev_201806_15162 29917191
     [Google Scholar]
  37. FukuokaT. YashiroM. KinoshitaH. MorisakiT. HasegawaT. HirakawaT. AomatsuN. TakedaH. MaruyamaT. HirakawaK. P rostaglandin D synthase is a potential novel therapeutic agent for the treatment of gastric carcinomas expressing PPARγ.Int. J. Cancer201513751235124410.1002/ijc.29392 25516376
     [Google Scholar]
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PGD2/PTGDR2 Signaling Affects the Stemness of Gastric Cancer Stem Cells by Regulating Autophagy
Comb Chem High Throughput Screen 29, 141 (2026); https://doi.org/10.2174/0113862073372570250123091700
/content/journals/cchts/10.2174/0113862073372570250123091700
/content/journals/cchts/10.2174/0113862073372570250123091700
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  • Article Type:     Research Article
Keyword(s): autophagy; Gastric cancer; prostaglandin D2; PTGDR2; stem cells; stemness

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