Down-regulation of MFNG promotes the metastatic potential of lung adenocarcinoma by regulating TGF-β/Smad signaling.

Manic Fringe (MFNG), a fucose-specific β-1,3-N-acetylglucosaminyltransferase, is critically involved in different cancers. However, the potential role and underlying mechanism of MFNG in the progression of lung adenocarcinoma (LUAD) remain unclear. Here, we found that MFNG was significantly down-regulated in LUAD tissues compared with adjacent non-cancerous tissues. Moreover, its decreased expression was associated with aggressive LUAD characteristics, including high grade and poor prognosis. Functional studies revealed that MFNG deficiency promoted migratory and invasive capabilities as well as the epithelial-mesenchymal transition of LUAD cells in vitro and metastatic potential in vivo. Mechanistically, we found that MFNG silencing resulted in a remarkable activation of the TGF-β/Smad signaling pathway. Pharmacological treatment with a TGF-β receptor kinase inhibitor alleviated the progressive phenotypes of LUAD cells induced by MFNG loss. Together, our results reveal a potential mechanism by which MFNG regulates LUAD progression and suggest that patients with advanced LUAD exhibiting MFNG deficiency may benefit from TGF-β signaling inhibition.