复发转移是胃癌死亡的主要原因，揭示其转移机制并探寻新的治疗靶点是改善胃癌预后的关键。前期全外显子测序提示ROR2突变可能参与胃癌复发转移。研究发现，野生型ROR2可活化p-JNK，抑制Cullin1以促进胃癌转移。转录因子FoxO1可在转录水平上诱导Cullin1的表达。我们推测ROR2通过p-JNK/FoxO1/Cullin1通路参与促进胃癌转移，ROR2突变可能影响该通路的信号转导，但具体功能及调控机制尚不清楚。本项目拟通过双荧光素酶报告基因、染色质免疫沉淀、病理组织免疫组化及测序等体内外实验研究ROR2/p-JNK/FoxO1/Cullin1通路的内在调控网络，初步探索ROR2基因突变的作用及机制。本项目旨在深入阐明ROR2促进胃癌转移的机制，以及ROR2突变后生物学功能变化及机制改变，这对于明确胃癌复发转移机制、寻找有效的分子靶点、走出胃癌治疗困境具有重要理论意义和潜在应用价值。

The recurrence and metastasis are major causes of gastric cancer-related death. Therefore, revealing the mechanism of metastasis and exploring new therapeutic targets are essential for improving the prognosis of gastric cancer. Whole-exome sequencing revealed that ROR2 mutations may be involved in the recurrence and metastasis of gastric cancer. It was found that wild type ROR2 could activate p-JNK and inhibit Cullin1 to enhance gastric cancer metastasis. Transcription factor FoxO1 can induce Cullin1 expression at the transcriptional level. We hypothesized that ROR2 might promote gastric cancer metastasis via ROR2/p-JNK/FoxO1/Cullin1 pathway, and the ROR2 mutation may affect the signaling pathway to mediate gastric cancer metastasis, however, the specific functions and regulation mechanisms are not clear. This project has planned to conduct the experiments such as dual luciferase reporter gene, chromatin immunoprecipitation, immunohistochemistry, and sanger sequencing to explore the underlying intrinsic molecular mechanisms of ROR2/p-JNK/FoxO1/Cullin1 pathway, and preliminary explore the effect of ROR2 mutation on the function and possible mechanism of the gene. Our study aims to elucidate the mechanism of ROR2 promoting gastric cancer metastasis, and biological function and its mechanism alteration after mutation, which is of great theoretical significance and potential application value for exploring effective molecular targets and getting out of treatment dilemma.