SSTR2在90%以上的胰腺癌中缺失表达，是胰腺癌潜在治疗位点,但受生物制剂安全性的制约，该位点一直无法用于临床治疗。在探索其下游有效治疗靶点的研究中，我们发现SSTR2调控Rho亚家族蛋白活性，但不依赖经典ROCK途径，可能通过特殊的蛋白位点调控胰腺癌生物学行为。Rho亚家族是肿瘤药物开发的热点蛋白家族，进一步阐明SSTR2与Rho亚家族的关系并明确其关键蛋白位点，对实现SSTR2临床应用转化具有重要意义。本项目拟在前期研究基础之上：检测Rho亚家族信号通路在胰腺癌中的特殊表达，免疫共沉淀技术阐明SSTR2与Rho亚家族信号通路的关系；基因芯片和蛋白质组学技术明确SSTR2-Rho亚家族下游关键蛋白；病毒载体及相关阻滞剂阐明它们对胰腺癌生物学特性的影响；对关键蛋白位点进行体内外干预明确其治疗作用。本项目将有望阐明SSTR2在胰腺癌生物学行为中的作用机制，为开发新的胰腺癌治疗药物奠定基础。

The loss of SSTR2 expression occurred in more than 90% of pancreatic cancer, and it is a potential pancreatic cancer treatment site. However, it has been unable to be applied into clinic for security constraints of biological agents. Aimed to explore SSTR2 effective downstream targets, our research group found that SSTR2 could regulate Rho subfamily protein activity, which not depend on classic ROCK pathway ,but might through certain spcific protein location to regulate the biological behavior of pancreatic cancer. Rho subfamily is a hot spot in anti-cancer drug development, and it's significantly meaningful to go a step further clarify the relationship between the SSTR2-Rho and figure out the key proteins location for applying SSTR2 into clinical practice. Based on the previous work, our project propose to detect Rho subfamily specific expression in pancreatic cancer, and clarify the relationship between SSTR2 and Rho subfamily signaling pathway by co-immunoprecipitation, and figure out SSTR2-Rho downstream key proteins by DNA microarray and proteomics technology, and clarify the Rho subfamily signaling pathway downstream key proteins affect the biological characteristics of pancreatic cancer by viral vectors and inhibitors. Furthermore, we propose to determine the therapeutic effect of SSTR2 by intervening the key target proteins location in vivo and in vitro.The project is expected to go a step further clarify the mechanism of how SSTR2 affect the malignant biological behavior in pancreatic cancer and establish the foundation for developing novel anti-pancreatic cancer drugs.