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目的 研究WWCs(WW and C2 Domain containing protein family)及其各亚型(WWC1,WWC2,WWC3)在人类肺癌中的表达是否存在差异、与临床病理因素的关系及其发挥生物学作用的相关机制.方法 应用免疫组化方法检测了159例非小细胞肺癌组织标本中WWCs蛋白表达和亚细胞定位,并对比分析与上皮间质转化相关蛋白E-cadherin、N-cadherin表达的关系.利用集落形成实验和transwell实验,检测WWC3对肺癌细胞增殖及侵袭能力的影响.转染或干扰WWC3的表达后,通过Western blot检测双向调控WWC3对E-cadherin、N-cadherin及Snail表达水平的影响.结果 WWC3在正常支气管上皮细胞浆中高表达(31/40,77.5％),而在非小细胞肺癌中低表达(70/159,44％),明显低于正常支气管上皮的阳性表达率(P＜0.001),且其低表达与非小细胞肺癌的低分化(P=0.0 10)、高TNM分期(P=0.016)、淋巴结转移(P=0.002)相关.WWC3的低表达与上皮间质转化相关蛋白E-cadherin的高表达(P=0.032)、N-cadherin的低表达(P=0.007)相关.在H1299细胞中转染WWC3表达质粒,抑制肺癌细胞的增殖与侵袭能力,下调Snail和N-cadherin,上调E-cadherin的表达.在A549细胞中转染WWC3-siRNA能够明显促进肺癌细胞的增殖和侵袭能力,上调Snail和N-cadherin的表达,而下调E-cadherin的表达.结论 WWC3抑制肺癌细胞侵袭和转移可能与下调Snail和N-cadherin,上调E-cadherin的表达相关.“,”Objective To study the expressions and clinicopathological significance of WWCs (WW and C2 domain containing) and the subtypes(WWC1,WWC2,WWC3) in human non-small-cell lung cancer.Methods The Immunohistochemical staining was used to check WWCs protein expression in human non-small-cell lung cancer.Colony forming experiment and transwell experiment were used to check WWCs influence on lung cancer cell proliferation and invasion.Western blot was used to check the expression of E-cadherin,N-cadherin and Snail.Results WWC3 was expressed highly in normal bronchial cytoplasm(31/40,77.5％),lower in lung cancer cells (70/159,44％,P＜0.001),and related to low differentiation (P=0.010) and high TNM stage (P=0.016) and lymph node metastasis(P=0.002),also related to the expression of E-cadherin(P=0.032) and N-cadherin(P=0.007).WWC3 expression plasmid transfection inhibited the proliferation and invasion ability of H1299 cells,downregulated Snail and N-cadherin expression,upregulated E-cadherin expression;but transfected WWC3-siRNA promoted the proliferation and invasion of A549 cells,upregulated Snail and Ncadherin expression,downregulated E-cadherin expression.Conclusion The inhibition of WWC3 on the invasion and metastasis of lung cancer cells might be related to down-regulating the expression of Snail and N-cadherin,up-regulating the expression of E-cadherin.