转移是我国高发胃癌致死的主要原因，EMT是转移起始阶段的重要机制。团队最新实验显示：①在已有转移的胃癌组织中PTPRO表达显著降低；②PTPRO下调导致Twist表达增多、E-cadherin表达减少；生物信息学与最新文献支持：① JAK/STAT3是PTPRO的下游信号通路，HER2是PTPRO的靶点分子；② HER2在有转移的胃癌组织表达率明显高于无转移晚期胃癌。据此，团队提出假说：PTPRO是HER2阳性胃癌中控制转移起始的重要基因，通过HER2/STAT3/Twist通路调节E-cadherin是其干预EMT和转移的分子机制。为证实假说，团队拟 ①扩大临床标本明确PTPRO表达与HER2阳性胃癌转移的关系；②应用细胞实验与活体成像技术，在体内外明确PTPRO是控制HER2阳性胃癌转移起始的开关；③分子水平证实PTPRO通过HER2/STAT3/Twist信号通路干预EMT和转移起始

Gastric cancer carries a poor prognosis that is largely attributable to early and.frequent metastasis, in which epithelial-mesenchymal transition (EMT) is one.essential mechanism that occurs at the initial stage. Our previous study has.demonstrated suppression of the gene for protein tyrosine phosphatase.receptor-type O (PTPRO) involved in esophageal squamous cell carcinoma. The latest.results in our laboratory showed that ① PTPRO protein expression was.significantly decreased in metastatic gastric cancer tissues; ② ectopic.expression of PTPRO in gastric cancer cells inhibited cell malignant invasiveness. Our .biology information analysis showed that ①JAK/STAT3 is the downstream signal pathway of PTPRO and HER2 is one main target gene; ② The expression of HER2 in.GC with metastasis was higher than that in the advanced GC without metastasis..Consequently, we hypothesize that PTPRO is one of the master genes which.regulate EMT and metastasis in gastric cancer. On the basis of our original.preliminary work, we investigate the effect and molecular mechanism of PTPRO on.gastric cancer metastasis by ① testing whether PTPRO is the switch to control.metastasis initiation using in intro cell culture experiments and in vivo.fluorescence imaging technology; ② evaluating PTPRO-regulated HER2/STAT3/Twist.signaling pathway during EMT and metastasis initiation; and ③ examining clinical.specimens and analyzing the potential relationship between PTPRO expression and.gastric cancer metastasis or prognosis. The present study, aiming at the initial.stage of metastasis, is to identify the original molecular mechanism for gastric.cancer metastasis, which might contribute to reveal the regulation of gastric.cancer metastasis as well as offer us new strategies for drug discovery.