Vol.:(0123456789) 1 3 International Journal of Clinical Oncology https://doi.org/10.1007/s10147-020-01771-1 ORIGINAL ARTICLE YAP promotes self‑renewal of gastric cancer cells by inhibiting expression of L‑PTGDS and PTGDR2 Qingli Bie 1,2  · Xiaozhe Li 1  · Shiqi Liu 3  · Xiao Yang 1  · Zhenwen Qian 1  · Rou Zhao 1  · Xiaobei Zhang 4  · Bin Zhang 1,2 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 gas- tric 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 confrmed that the expression of YAP mRNA and protein in GC tissues was higher than in adjacent tissues by RT-PCR, western blot and immunohistochemistry. Immunofuorescence 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 spheri- cal 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 confrmed 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 efect 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 According to GLOBOCAN 2018, gastric cancer is the ffth malignant tumor and the cause of the third tumor-related death [1]. Gastric antrum cancers and gastric carcinomas are most common cancer among GCs; however, the incidence of gastroesophageal junction carcinomas is gradually increas- ing [2, 3]. East Asian countries are considered areas with high incidence of GCs, particularly Japan and China [4]. Despite the therapy of GCs has advanced in recent decades, the prognosis of GC remains poor, because most patients have reached the advanced stage when they are diagnosed with gastric cancer, and current chemotherapy only improve the survival time of patients [5]. Therefore, it is necessary to identify novel targets and signaling molecules involved in the tumorigenesis and progression of gastric cancer. Yes-associated protein 1 (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are important downstream transcription factors of the Hippo pathway [6]. 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 zhb861109@163.com 1 Department of Laboratory Medicine, Afliated 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, Afliated Hospital of Jining Medical University, Jining, Shandong, People’s Republic of China 4 Department of Central Laboratory, Afliated Hospital of Jining Medical University, Jining, Shandong, People’s Republic of China