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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Cancer Molecular Targets and Therapeutics
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1496050

PGD2/PTGDR2 signaling pathway affects the self-renewal capacity of gastric cancer stem cells by regulating ATG4B ubiquitination

Provisionally accepted
Qiang Zhang Qiang Zhang 1恒金 田 恒金 田 1Kunpeng Ge Kunpeng Ge 2Feifan Wang Feifan Wang 3Peiyao Gao Peiyao Gao 2Amin Chen Amin Chen 1Lulu Wang Lulu Wang 1Yanming Zhao Yanming Zhao 4Chaoqun Lian Chaoqun Lian 2Fengchao Wang Fengchao Wang 1*
  • 1 The First Affiliated Hospital of Bengbu Medical College, Handan, China
  • 2 Bengbu Medical College, Bengbu, Anhui Province, China
  • 3 Department of Blood Transfusion, Changzheng Hospital, Naval Medical University (Second Military Medical University), Huangpu, Shanghai, China
  • 4 Bengbu Third People's Hospital, Bengbu, Anhui Province, China

The final, formatted version of the article will be published soon.

    Prostaglandin D2 (PGD2) inhibits the development of different malignant tumors; however, the underlying mechanism of inhibiting tumor development is not yet clear. This study aimed to elucidate how PGD2 inhibits the stemness of gastric cancer stem cells (GCSCs) via autophagy and its underlying molecular mechanism to provide a theoretical basis for the treatment of gastric cancer.In this study, GCSCs were enriched in vitro by serum-free incubation. Furthermore, the effects of PGD2 and PGD2 receptor (PTGDR2) on autophagy were detected by Western blotting, immunofluorescence analysis, and transmission electron microscopy. Moreover, the ATG4B ubiquitination levels were assessed via immunoprecipitation and other methods.The results indicated that PGD2 induced LC3I/LC3II conversion in GCSCs to activate autophagy, while PGD2 promoted the expression of PTGDR2, thereby further activating autophagy. Furthermore, PTGDR2 competes with ATG4B for binding with E3 ligase RNF5 (also known as RMA1) to promote autophagy protein ATG4B expression. Moreover, PTGDR2 knockdown blocked the activation of autophagy by PGD2 and the level of ATG4B ubiquitination in GCSCs.In summary, it was elucidated that the PGD2/PTGDR2 signaling cascade affects GCSCs stemness by regulating autophagy, suggesting that the PGD2/PTGDR2 signaling pathway could serve as a novel target for cancer therapy.

    Keywords: gastric cancer, cancer stem cells, PTGDR2, Autophagy, Ubiquitination

    Received: 13 Sep 2024; Accepted: 02 Dec 2024.

    Copyright: © 2024 Zhang, 田, Ge, Wang, Gao, Chen, Wang, Zhao, Lian and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Fengchao Wang, The First Affiliated Hospital of Bengbu Medical College, Handan, China

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