IL-6 promotes metastasis and EMT of non-small cell lung cancer cells by up-regulating FGL1 via STAT3 pathway

It has been reported that IL-6 induces the synthesis and secretion of fibrinogen-like protein 1 (FGL1) in liver cells as well as promotes the regeneration of liver cells. FGL1 is upregulated in human cancers, especially in non-small cell lung cancer (NSCLC). FGL1 is involved in the regulation of epithelial-mesenchymal transition (EMT) in gastric cancer (GC) cells. However, the role of IL-6/FGL1 signaling axis in the EMT process of NSCLC cells and its mechanism remain unclear. In this study, we investigated the role of FGL1 in mediating the metastasis and EMT processes of NSCLC cells, as well as the underlying signaling mechanisms. The Cancer Genome Atlas (TCGA) database and STARBASE database were used to analyze the biological information of FGL1 gene expression in NSCLC patients, and the database information was verified by clinical data. Transwell, Western blotting and microscopy were used to observe the effects of FGL1 on the metastasis and proliferation of NSCLC cells and the occurrence of EMT and its potential signaling pathway proteins. Database analysis and clinical data showed that the prognosis of NSCLC patients with high FGL1 expression was poor. Cell phenotypic experiments showed that FGL1 silencing significantly reduced proliferation, migration and EMT of NSCLC cells, suggesting that the expression level of FGL1 may be significantly correlated with migration ability and EMT in lung cancer cells. In addition, the FGL1-neutralizing antibody inhibited EMT and metastasis of NSCLC cells in vivo. Further studies showed that IL-6 may mediate EMT by inducing FGL1 expression through the STAT3 pathway in lung cancer cells. Furthermore, treatment with a STAT3 inhibitor significantly inhibited the IL-6-induced FGL1 expression and EMT in NSCLC cells. IL-6 regulates FGL1 expression to mediate metastasis and EMT of NSCLC cells through the STAT3 signaling pathway.