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YAP promotes self-renewal of gastric cancer cells by inhibiting expression of L-PTGDS and PTGDR2

Abstract

Introduction

Cancer stem cells have been implicated angiogenesis of tumor and invasiveness, drug resistance in tumors. Yes-associated protein 1 (YAP) owns carcinogenic roles in various organs, but the role of YAP in cancer stem cells of gastric cancer (GC) remains unclear. In this study, we explored the function and mechanism of YAP in GC cancer stem cells.

Materials and methods, and results

First, we confirmed that the expression of YAP mRNA and protein in GC tissues was higher than in adjacent tissues by RT-PCR, western blot and immunohistochemistry. Immunofluorescence staining of the GC tissues revealed that the region of YAP expression coincided with the region of expression of the cancer stem cell marker SALL4 but did not overlap with that of the epithelial marker cytokeratin 14 (CK14). Additional research revealed that spherical cells expressed relatively high levels of YAP protein, and YAP overexpression reinforced self-renewal and expression of stem cell markers in the GC cells. Knockdown the expression of YAP reversed this phenomenon. Second, we examined the expression patterns of lipocalin-type prostaglandin D2 synthase (L-PTGDS) and prostaglandin D2 receptor 2 (PTGDR2) in GC tissues and proved that there was negatively correlation between the expression of L-PTGDS and PTGDR2 and YAP in GC tissues. Finally, we confirmed that YAP inhibited the expression of L-PTGDS and PTGDR2 by gain- and loss-of-function experiments. Moreover, the overexpression of L-PTGDS and PTGDR2 suppressed the proliferation and self-renewal induced by YAP in vitro and reversed the pro-tumor effect of YAP in vivo.

Conclusion

Our results revealed a novel function of YAP and the mechanism underlying cancer stem cell regulation by YAP.

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Data availability

The various raw data and methods used to support the findings of this study are available from the corresponding author upon request.

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Acknowledgements

This study was supported by grants from National Natural Science Foundation of China (No. 81702439, 81802446), Tai Shan Young Scholar Foundation of Shandong Province (NO.tsqn201909192), Shandong Provincial Natural Science Foundation (No. ZR2019BH050). Supported by PhD Research Foundation of Affiliated Hospital of Jining Medical University (No. 2018-BS-001, 2018-BS-013), the Project of Health and Family Planning Commision of Shandong province (NO. 2017WS513), Supporting Fund for Teachers' research of Jining Medical University (NO.JYFC2018FKJ035). This manuscript was edited by Wallace Academic Editing.

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The authors declare no competing financial interests.

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Correspondence to Bin Zhang.

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Bie, Q., Li, X., Liu, S. et al. YAP promotes self-renewal of gastric cancer cells by inhibiting expression of L-PTGDS and PTGDR2. Int J Clin Oncol 25, 2055–2065 (2020). https://doi.org/10.1007/s10147-020-01771-1

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Keywords

  • Yes-associated protein 1
  • Prostaglandin D2 synthase
  • Prostaglandin D2 receptor 2
  • Gastric
  • Cancer stem cell