N-端RASSFs蛋白的作用和机制尚在探讨之中。我们发现分子相近的RASSF7和10在肺癌中的表达、定位及临床意义均不同，双向调控表达后发现它们对肺癌细胞的增殖和侵袭能力的影响是相反的。免疫共沉淀结果发现RASSF7与MST1，而RASSF10与p-LRP6相互作用。我们提出RASSF7和10中的2个CC结构域具有经典RASSFs中SARAH结构域类似的功能，但因2个CC结构域相距不同，造成RASSF7抑制Hippo而RASSF10抑制Wnt通路活性的作用。本研究拟在双向调控RASSF7和10表达，构建和转染可能影响它们功能的各种结构域的突变质粒和互换结构质粒，结合荧光素酶报告基因和GST Pull-Down等方法，揭示RASSF7和10通过Hippo和Wnt信号通路发挥作用的分子机制，并对它们的功能和机制进行验证。研究将为了解Ras突变相关肿瘤发病、耐药机制以及新药研制提供新的思路。

N-terminal RASSFs (Ras-association domain family) are new members of the RASSFs, which function differently in cellular pathophysiology through distinct pathways. Though sharing similar domains, RASSF7 and RASSF10 behave oppositely in affecting NSCLC cell malignant behavior. Histologically, their expression and localization are of different clinical significances. We found out by immunoprecipitation that RASSF7 can interact with MST1, meantime RASSF10 can interact with phosphorylated LRP6. We brought up that the coiled-coil domains in RASSF7 and RASSF10 share some similarities with the SARAH domain in MST1, however, the distance between the two coiled-coils in RASSF7 is much shorter than that in RASSF10, leading to the functional diverse between these two proteins: RASSF7 overexpression can inhibit Hippo signaling pathway whereas RASSF10 upregulation can inhibit Wnt signaling pathway. This study will both up and down regulate the expression of RASSF7 and RASSF10, transfect those theoretically functional spliced plasmids as well as reconstructed plasmids, to reveal the molecular mechanisms of RASSF7-Hippo and RASSF10-Wnt interaction by means of luciferase report, immunoprecipitation and GST pull-down experiment, etc. We will also confirm our hypothesis in experiments like western blot, colony formation and MTT assay, Matrigel invasion assay, real-time PCR and nude mice tumor cell transplantation. This project will provide us a brand-new aspect of the mechanism regarding ras-associated tumorigenesis, drug resistance and new drug discovery.