TROP2通过内质网上“Ca2+-Fe2+交换”调控PLOD2来重塑肿瘤微环境

我国胃癌发病例数和死亡例数约占全球胃癌发病和死亡的一半左右，已经成为严重威胁我国人群健康的主要公共卫生问题之一。肿瘤个体异质性和复杂的肿瘤微环境导致靶向药物适用受限，因此有效的肿瘤靶向药物研制迫在眉睫。课题组前期研究发现TROP2与PLOD2有密切相关性，随后通过人体病理组织、细胞学和动物实验三个方面证明PLOD2在胃癌中的表达情况与预后相关及对胃癌侵袭转移的影响。并提出PLOD2上游可能受TROP2的钙离子信号转导通路“内质网Ca2+-Fe2+交换”调控促进肿瘤的侵袭转移并影响肿瘤细胞能量代谢和微环境的科学假说。本研究利用蛋白质谱分析、CO-IP、pull-down及组织芯片天狼星红、Masson三色染色等方法进行PLOD2与TROP2之间分子调控机制的研究，为胃癌侵袭转移的分子机制提供一个新的思路，为PLOD2和TROP2作为胃癌新的治疗靶标提供理论基础。

The number of cases and deaths of gastric cancer in China accounts for about half of the incidence and death of gastric cancer in the world, which has become one of the major public health problems that seriously threaten the health of the population in our country. Tumor individual heterogeneity and complex tumor microenvironment limit the application of targeted drugs, so it is urgent to develop effective tumor targeted drugs. The previous study of our group found that there was a close correlation between TROP2 and PLOD2. Then through human pathological tissue, cytology and animal experiments, it was proved that the expression of PLOD2 in gastric cancer was related to prognosis and its effect on invasion and metastasis of gastric cancer. It is also proposed that the upstream of PLOD2 may be regulated by TROP2 calcium signal transduction pathway "endoplasmic reticulum Ca2+-Fe2+ exchange" to promote tumor invasion and metastasis and affect tumor cell energy metabolism and microenvironment. In this study, protein spectrum analysis, CO-IP, pull-down and tissue microarray Sirius red and Masson trichrome staining were used to study the molecular regulation mechanism between PLOD2 and TROP2, so as to provide a new idea for the molecular mechanism of invasion and metastasis of gastric cancer and provide a theoretical basis for PLOD2 and TROP2 as new therapeutic targets for gastric cancer.