ABSTRACT
Background and Objective: Metastasis is the leading cause of death in patients with advanced non-small cell lung cancer (NSCLC), and epithelial-mesenchymal transition (EMT) is a crucial event in the metastasis of NSCLC. Our previous works demonstrated that NgBR promoted EMT in NSCLC. However, the molecular mechanism was unclear. Methods: TGF-ß1 was used to induce EMT process of NSCLC cells. The biological functions of NgBR in promoting TGF-ß1-induced NSCLC metastasis were studied by gain- and loss-of-function assays both in vitro and in vivo. The underlying mechanisms were studied using molecular biology assays. Results: We found that knockdown of NgBR inhibited TGF-ß1-induced cell migration and invasion in NSCLC cells. In contrast, NgBR overexpression promoted TGF-ß1-induced EMT of A549 cells. Mechanically, we found that knockdown of NgBR facilitated ubiquitination and degradation of TßRI, leading to downregulation of TßRI expression in NSCLC cells. Moreover, we confirmed a positive correlation between NgBR and TßRI in NSCLC tissues. Conclusions: Our findings provide a novel role of NgBR in modulating TGF-ß1-induced EMT and propose NgBR as a new therapeutic target for treating NSCLC patients.
