FBXW7 suppresses epithelial-mesenchymal transition and chemo-resistance of non-small-cell lung cancer cells by targeting snai1 for ubiquitin-dependent degradation

ObjectivesFBXW7 acts as a tumour suppressor by targeting at various oncoproteins for ubiquitin-mediated degradation. However, the clinical significance and the involving regulatory mechanisms of FBXW7 manipulation of NSCLC regeneration and therapy response are not clear. Materials and MethodsImmunohistochemical staining and qRT-PCR were applied to detect FBXW7 and Snai1 expression in 100 samples of NSCLC and matched tumour-adjacent tissues. FBXW7 manipulation of cancer biological functions were studied by using MTT assay, immunoblotting, flow cytometry, transwells, wound healing assay, and sphere-formation assays. Immunofluorescence and co-immunoprecipitation were used to analyse the possible interaction between Snai1 and FBXW7. ResultsWe detected the decreased FBXW7 expression in majority of the NSCLC tissues, and lower FBXW7 level was correlated with advanced TNM stage. Furthermore, those patients with decreased FBXW7 expression tend to have both poorer 5-year survival outcomes, and shorter disease-free survival, comparing to those with higher FBXW7 levels. Functionally, we found that FBXW7 enforcement suppressed NSCLC progression by inducing cell growth arrest, increasing chemo-sensitivity and inhibiting Epithelial-mesenchymal Transition (EMT) progress. Results further showed that FBXW7 could interact with Snai1 directly to degrade its expression through ubiquitylating alternation in NSCLC, which could be partially abrogated by restoring Snai1 expression. ConclusionsFBXW7 conduction of tumour suppression was partly through degrading Snai1 directly for ubiquitylating regulation in NSCLC