YAP promotes self-renewal of gastric cancer cells by inhibiting expression of L-PTGDS and PTGDR2
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ORIGINAL ARTICLE
YAP promotes self‑renewal of gastric cancer cells by inhibiting expression of L‑PTGDS and PTGDR2 Qingli Bie1,2 · Xiaozhe Li1 · Shiqi Liu3 · Xiao Yang1 · Zhenwen Qian1 · Rou Zhao1 · Xiaobei Zhang4 · Bin Zhang1,2 Received: 8 May 2020 / Accepted: 10 August 2020 © Japan Society of Clinical Oncology 2020
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. Keywords Yes-associated protein 1 · Prostaglandin D2 synthase · Prostaglandin D2 receptor 2 · Gastric · Cancer stem cell
Introduction Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10147-020-01771-1) contains supplementary material, which is available to authorized users. * Bin Zhang [email protected] 1
Department of Laboratory Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, 89 Guhuai Road, Jining 272000, Shandong, People’s Republic of China
2
Institute of Forensic Medicine and Laboratory Medicine, Jining Medical University, Jining, Shandong, People’s Republic of China
3
Department of General Surgery, Affiliated Hospital of Jining Medical University, Jining, Shandong, People’s Republic of China
4
Department of Central Laboratory, Affiliated Hospital of Jining Medical University, Jining, Shandong, People’s Republic of China
According to GLOBOCAN 2018, gastric cancer is
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