Knockdown of 14-3-3γ Suppresses Epithelial-Mesenchymal Transition and Reduces Metastatic Potential of Human Non-small Cell Lung Cancer Cells.

Abstract

14-3-3γ is involved in the metastasis of lung cancer cells. However, its functional roles in tumor cell invasion and the underlying mechanisms are still not understood. In this study, the roles and molecular mechanisms of 14-3-3γ in epithelial-mesenchymal transition (EMT), migration, and invasion were investigated using A549 and H358 non-small cell lung cancer (NSCLC) cell lines. siRNA against 14-3-3γ was used to suppress 14-3-3γ expression. Expression levels of proteins were detected by western blotting. Activity of matrix metalloproteinases (MMP)-2 and MMP9 was determined by gelatin zymography. Cell migration and invasion were analyzed using the Transwell assay. Knockdown of 14-3-3γ resulted in a significant reduction of expression of EMT-associated proteins in NSCLC cell lines, and led to significant reduction in invasion and migration by approximately 59% and 39% in A549 cells, and 65% and 62% in H358 cells, respectively. In addition, MMP2 and MMP9 activity was significantly reduced in both NSCLC cell lines after down-regulation of 14-3-3γ. Our results suggest that knockdown of 14-3-3γ may be a potential strategy for suppressing metastasis of lung cancer by inhibiting MMP2 and MMP9 through regulation of EMT.