胃癌发病率高、预后差，胃癌干细胞是导致肿瘤异质性和转移复发的重要原因。我们通过原代胃癌干细胞蛋白质谱率先发现硬脂酰辅酶A去饱和酶1（SCD1）在胃癌干细胞中显著高表达，提示SCD1是胃癌干细胞的新标志物。生物信息学分析和临床标本表达检测等多个实验初步证实SCD1通过YAP通路影响胃癌干细胞特性。本课题拟在前期研究基础上，开展如下研究：①免疫组化、免疫蛋白印迹等探究SCD1表达及其与YAP通路蛋白表达的相关性；②探究小干扰RNA和化学抑制剂下调SCD1表达对胃癌干细胞体外成球、化疗耐药、侵袭转移、EMT现象、免疫缺陷小鼠成瘤及体内转移等干细胞特性的影响；③Co-IP等技术探究YAP通路关键蛋白相互作用关系及分子机制。本项目将首次阐明SCD1通过YAP通路调控胃癌干细胞干性的分子机制，拓展胃癌干细胞理论认知，为以SCD1为靶点的肿瘤治疗和药物开发提供新依据。

Gastric cancer is one of malignant tumor with high incidence and poor prognosis. Cancer stem cells are an important cause of tumor heterogeneity and metastasis. Our previous study revealed that Stearoyl-CoA desaturase 1(SCD1) was significantly upregulated in gastric cancer stem cells via proteome analysis, suggesting that SCD1 is a new marker of gastric cancer stem cells. Several experiments, such as bioinformatics analysis and clinical specimen expression detection, have initially confirmed that SCD1 regulates stem-like properties through Hippo/YAP signaling pathway. Based on these preliminary results, in this proposal, we will carry out the following research: ①To investigate the SCD1 expression and association between SCD1 and YAP by IHC and WB; ②To investigate whether SCD1 affect the stem-like properties, including sphere forming ability, chemo-resistance, tumor invasion, EMT transition, xenogragft tumor growth, by SCD1 inhibition or not; ③To explore how SCD1 regulates biological behavior via Hippo/YAP pathway by GSEA, WB analysis and Co-IP analysis, etc. This study would help illuminate the role of SCD1 in regulating gastric cancer stem cells through altered Hippo pathway and expand the theoretical understanding of gastric cancer stem cells, providing a new basis for tumor therapy and drug development by targeting SCD1.