STIP1通过调控EGR1促进胃癌化疗抵抗与转移的机制研究

After comprehensive treatment of gastric cancer, the risk of chemotherapy resistance, recurrence and metastasis is high, which seriously affects the prognosis of patients, but the specific molecular mechanism is still unclear. Our previous research found that stress-induced phosprotein 1 (STIP1) is highly expressed in gastric cancer and is closely related to its prognosis. It can promote the epithelial mesenchymal transformation (EMT) of gastric cancer cells and upregulate expression of the early growth response factor 1 (EGR1), and promote the repair of 5-FU-induced DNA damage through homologous recombination repair pathways, up-regulate the expression of chemotherapy resistance-related genes, and enhance the ability of chemotherapy resistance. Therefore, we propose the working hypothesis of this project: STIP1 promotes homologous recombination repair of DNA damage and EMT by targeting EGR1 to enhance chemotherapy resistance and invasion and metastasis ability of gastric cancer cells. This project intends to further investigate whether STIP1 can activate Wnt signaling pathway by targeting EGR1 to promote chemotherapy resistance and the ability of invasion and metastasis of gastric cancer cells. The research will help to reveal the specific mechanism of chemotherapy resistance, invasion and metastasis of gastric cancer, and provide a theoretical basis for precise medical treatment of gastric cancer.

胃癌综合治疗后出现化疗抵抗与复发转移的风险高，严重影响患者的预后，但其具体的分子机制尚不清楚。我们前期研究发现应激诱导磷酸化蛋白1（STIP1）在胃癌患者中高表达，并与其预后密切相关，可促进胃癌细胞的上皮间充质转化（EMT），上调早期生长反应因子1（EGR1）的表达，并通过同源重组修复途径促进5-FU诱导的DNA损伤修复，上调化疗抵抗相关基因的表达，增强化疗抵抗能力，因此我们提出本项目的工作假设：STIP1通过靶向调控EGR1促进胃癌细胞发生DNA损伤的同源重组修复与EMT，增强胃癌细胞的化疗抵抗与侵袭转移能力。本项目拟进一步研究STIP1是否通过靶向EGR1激活Wnt信号通路，促进胃癌化疗抵抗与侵袭转移。研究成果将有助于揭示胃癌发生化疗抵抗、侵袭转移的具体机制，为胃癌的精准治疗提供理论依据。