转移和化疗耐药是导致胃癌不良预后的重要因素，故揭示胃癌转移及耐药机制，寻找新的治疗靶点，是改善胃癌预后、提高胃癌患者的生存率的关键。本项目前期研究发现维甲酸相关孤核受体γ(RORC)是胃癌潜在的抑癌基因，既能抑制胃癌细胞的侵袭转移，又能增强胃癌细胞的化疗敏感性；同时发现RORC对Twist1这一上皮细胞间质转化(EMT)过程中的重要转录因子具有调控作用。据此，本项目在前期工作基础上推断RORC可能通过Twist1调控EMT来调节胃癌细胞转移与化疗敏感性。为了证实这一推断，本项目拟利用分子克隆、双荧光素酶报告基因、基因/组织芯片、小动物活体成像等体内外实验，研究RORC/Twist信号轴的内在调控网络及其调控胃癌转移和化疗敏感性的作用机制。这项研究对明确胃癌转移和耐药机制，寻找可用于胃癌的治疗干预靶点和预后判断指标具有重要的理论意义和潜在临床转化价值。

Gastric cancer is liable to metastasis and chemoresistance, which results in bad therapeutic effect and higher mortality, so revealing of metastasis and chemoresistance mechanism and exploring of new therapeutic targets have become one of the key problems urgently to be solved in gastric cancer treatment. Through high throughput screening, we found that retinoid acid receptor-related orphan receptor γ (RORC) was a potential tumor suppressor gene in gastric cancer, which not only inhibited gastric cancer cell metastasis, but also increased cell chemosensitivity. Further study indicated that RORC might exert its effect on cell metastasis and chemosensitivity by regulating the program of epithelial-mesenchymal transition through regulating the expression of Twist1, but the underlying mechanism remains unclear. Therefore, based on our previous works, this study will use in vivo and in vitro experiments, such as dual luciferase report gene, gene/tissue chips and small animal in vivo imaging and immunohistochemical staining, to explore the underlying intrinsic molecular mechanisms of RORC/Twist1 signaling axis and the role in metastasis and chemoresistance of gastric cancer. Our study may further explore the molecular mechanism of metastasis and chemoresistance of gastric cancer and identify critical molecular targets for the prognosis and therapy, which may have the important theoretical significance and the potential value.