Pathological Significance Of LATS1 Expression In Head And Neck Squamous Cell Carcinoma And Its Effect On Cell Proliferation And Invasion

Objective: To evaluate the clinicopathological significance of LATS1 expression and its correlation with overall survival and clarify the effects of Large Tumor Suppressor 1(LATS1)on proliferation,migration,invasion and epithelial-mesenchymal transition in HNSCC.Methods: Normal Squamous epithelium,dysplasia and carcinoma samples were collected to analysis the expression of LATS1 in these samples by Immunohistochemistry.Clinicopathological data were collected to analyze the relationship between LATS1 expression and clinicopathological parameters.In the other hand,the recombinant plasmid vector p CDNA3.1-LATS1 contained LATS1 gene sequences was constructed and transfected into B88 cells.The expression of LATS1 protein was validated by western blotting.The cell proliferation was assayed by MTT assay;Transwell chamber test was used to analyze migration and invasion.Then,the effects of LATS1 on Epithelial-mesenchymal transition(EMT)associated protein,such as β-catenin,E-cadherin,N-cadherin,Twist,MMP-2,MMP-9 and ZEB-2,were detected by western blotting.Results: Immunohistochemistry showed that LATS1 was downregulated in HNSCC.Cytoplasmic LATS1 expression was much more positive in carcinoma than in normal squamous tissue(P < 0.05)but versa for Nuclear counterpart(P < 0.05).In HNSCC,Cytoplasmic LATS1 expression was positively correlated with lymph node metastasis(P <0.05).The recombinant plasmid vector p CDNA3.1-LATS1 was successfully constructed.Western blot showed that LATS1 protein was significantly increased in LATS1 transfectants(P< 0.05).MTT assay showed that LATS1 significantly inhibited proliferation in B88 cells(P< 0.05),Transwell assay showed that LATS1 significantly suppressed cell migration and invasion compared with the control and mock(P<0.05),and Western blot showed that the LATS1 upregulated the expression of β-catenin and E-cadherin,and downregulated the expression of N-cadherin,MMP-2,MMP-9,and Twist(P<0.05).Conclusion: In HNSCC,LATS1 was downregulated and LATS1 protein may be translocated from nucleus to cytoplasm,cytoplasmic LATS1 expression was correlated with lymph node metastasis.LATS1 can significantly inhibit the proliferation,migration,invasion and EMT in HNSCC.