WW和C2结构域蛋白家族（WWCs）中的WWC1可与Lats1结合激活Hippo通路，而WWC3在人类肿瘤的作用尚无报道。我们发现，WWC3的低表达与肺癌的淋巴结转移和不良预后相关，并且发现WWC3与Dvls存在相互作用。故提出Dvls可能与Lats1竞争性结合WWC3，抑制Hippo通路活性，促进肺癌细胞的恶性表型。我们拟双向调控WWC3和Dvls的表达，构建和转染WWC3与Lats1和Dvls结合位点的突变体等策略，采用免疫共沉淀，GST-Pull-Down，荧光素酶报告基因，实时定量PCR等方法，在体内外阐明WWC3-Dvl-Lats1相互作用模式和机制、对Hippo和Wnt通路活性的影响。揭示WWC3低表达和抑制非小细胞肺癌增殖、侵袭和转移的分子机制，为寻找新的非小细胞肺癌的生物标记及药物的开发提供实验基础。

WWC1 of WWCs family could interact with Lats1 and activate Hippo pathway. The roles of WWC3 in human tumors remain elusive. We found that WWC3 is downregulated in human non-small cell lung cancer and correlates with poor prognosis. WWC3 could interact with Dvls. We postulate that Dvls and Lats1 interact with WWC3 competitively, thus inhibit hippo signaling and promote malignant phenotype of lung cancer cells. We will upregulate and downregulate Dvls and WWC3 expression, construct and transfect WWC3 mutants which could not bind with Lats1 and Dvls, employ immunoprecipitation, GST pull-down, luciferase reporter assay and realtime RT-PCR, to elucidate the mode and mechanism of WWC3-Dvls-Lats1 interaction and its effect on Hippo and Wnt pathways. We will also try to explore the molecular mechanism of WWC3 downregulation and its effect on proliferation and invasion inhibition, which provides basis for development of new biomarker and drugs for non-small cell lung cancer.