KCTD11 Inhibits The Proliferation And Metastasis Of Lung Cancer By Binding To β-catenin To Regulate The Activity Of The Wnt Pathway And Hippo Pathway

Background:KCTD11 has been reported to be a potential tumor suppressor in several tumor types.However,the expression of KCTD11 and its role have not been reported in human nonsmall cell lung cancer(NSCLC).Whether its potential molecular mechanism is related to its BTB domain is also unknown.Methods:The expression of KCTD11 in 139 tissue samples with NSCLC was detected by immunohistochemistry and its correlation with clinicopathological factors was analyzed.The effect of KCTD11 on the biological behavior of lung cancer cells was verified in vitro and in vivo.The activity of Wnt pathway and Hippo pathway,the effect on epithelial-mesenchymal transition(EMT)process and the potential effect of KCTD11 on Wnt/β-catenin and Hippo/YAP pathway were observed by Western blot,dual-luciferase assay,RT-qPCR,immunofluorescence and Immunoprecipitation.Results:KCTD11 is under-expressed in lung cancer tissues and cells,and negatively correlated with degree of differentiation,Tumor-Node-Metastasis(TNM)stage,and lymph node metastasis.Low expression of KCTD11 was associated with poor prognosis.Overexpression of KCTD11 inhibited the proliferation and migration of lung cancer cells,and the results were reversed after knock down.Further studies indicated that KCTD11 inhibited Wnt pathway,activated Hippo pathway and inhibited EMT processes by inhibiting nuclear translocation of β-catenin and YAP.When we knocked down β-catenin,KCTD11 lost its stimulatory effect on the Hippo pathway.These findings confirm the interaction between KCTD11,β-catenin and YAP,further revealing the link between the Wnt and Hippo pathway.Conclusion:KCTD11 inhibits β-catenin and YAP nuclear translocation and inhibits the malignant phenotype of lung cancer cells by interacting with β-catenin,which provides an important experimental basis for the discovery of novel biomarkers of lung cancer and the development of highly effective targeted therapy.