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26.08.2020 | Original Article

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

verfasst von: Qingli Bie, Xiaozhe Li, Shiqi Liu, Xiao Yang, Zhenwen Qian, Rou Zhao, Xiaobei Zhang, Bin Zhang

Erschienen in: International Journal of Clinical Oncology | Ausgabe 12/2020

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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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Metadaten
Titel
YAP promotes self-renewal of gastric cancer cells by inhibiting expression of L-PTGDS and PTGDR2
verfasst von
Qingli Bie
Xiaozhe Li
Shiqi Liu
Xiao Yang
Zhenwen Qian
Rou Zhao
Xiaobei Zhang
Bin Zhang
Publikationsdatum
26.08.2020
Verlag
Springer Singapore
Erschienen in
International Journal of Clinical Oncology / Ausgabe 12/2020
Print ISSN: 1341-9625
Elektronische ISSN: 1437-7772
DOI
https://doi.org/10.1007/s10147-020-01771-1

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