Abstract
γ-Catenin (Plakoglobin), a well-described structural protein functioning at the adherens junctions and desmosomes, was shown to be either lost or weakly expressed in non-small cell lung cancer (NSCLC) cells and tumor tissues. However, the tumor suppressive affects of γ-catenin were not fully understood. In this study, we have identified a novel role for the affects of γ-catenin on non-small cell lung cancer (NSCLC) cell migration. Expression of γ-catenin in NSCLC cells resulted in reduced cell migration as determined by both scratch assays and trans-well cell migration assays. Moreover, the affects of γ-catenin on cell migration were observed to be p53-dependent. Mechanistically, the anti-migratory effects seen via γ-catenin were driven by the expression of hepatocyte growth factor activator inhibitor Type I (HAI-1 or SPINT-1), an upstream inhibitor of the c-MET signaling pathway. Furthermore, the re-expression of γ-catenin sensitized NSCLC cells to c-MET inhibitor-mediated growth inhibition. Taken together, we identify γ-catenin as a novel regulator of HAI-1, which is a critical regulator of HGF/c-MET signaling. Therefore, targeting γ-catenin-mediated HAI-1 expression might be a useful strategy to sensitize NSCLC to c-MET inhibitors.
Highlights
Background: ␥-Catenin is a tumor suppressor in lung cancer
In the current study we have identified a novel role for ␥-catenin in the regulation of cell migration, which is an important step for tumor progression and metastasis
We further evaluated the expression of ␥-catenin in an expanded panel of non-small cell lung cancer (NSCLC) cell lines via immunoblotting with ␥-catenin-specific antibodies (Fig. 1A) and observed a striking decrease in ␥-catenin expression in 82% of NSCLC cell lines tested when compared with a non-transformed bronchial epithelial cell line i.e. Beas2B (Fig. 1A)
Summary
Background: ␥-Catenin is a tumor suppressor in lung cancer. Results: ␥-Catenin is a novel regulator of HAI-1 and cell migration. F and G, migration of H157 and H1299 cells transfected with either control or ␥-catenin plasmids were assayed in trans-well inserts as described under “Experimental Procedures.” Top panel represents the number of cells migrated, while representative images were displayed in the bottom panel.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
