Anti-FOSL2 (full length) polyclonal antibody

Background: HGF/MET has been found to be associated with non-small cell lung cancer (NSCLC). However, the underlying molecular mechanisms of HGF/MET involved in regulating the metastasis of NSCLC remain unclear. Methods: The effect of HGF/MET and FOSL2 on cell migration and invasion were assessed by transwell and scratch assays. HGF/MET-induced phosphorylation and upregulation of FOSL2 was analyzed by RT-PCR and Western blotting. Regulatory effects of FOSL2 on SNAI2 transcription were detected by chromatin immunoprecipitation (ChIP) and dual-Luciferase reporter assays. The correlations of FOSL2 expression with clinical outcomes were assessed in 56 NSCLC patients. Results: HGF/MET induced the phosphorylation and upregulation of FOSL2 by ERK1/2 kinase, FOSL2 promoted the transcription of SNAI2 by binding with the SNAI2 promoter, and SNAI2 subsequently promoted the epithelial-mesenchymal transition (EMT), invasion, and migration of NSCLC cells. According to the clinical correlation analysis in NSCLC, high expression of FOSL2 correlated with advanced tumor stage and metastasis. Conclusion: Our studies propose that the regulatory mechanisms of the HGF/MET-induced cascade pathway is mediated by FOSL2 in NSCLC metastasis and suggested that FOSL2 could potentially be employed as a prognostic biomarker and potential therapeutic target of NSCLC metastasis.

Differentiating neutrophils undergo large-scale changes in nuclear morphology. How such alterations in structure are established and modulated upon exposure to microbial agents is largely unknown. Here, we found that prior to encounter with bacteria, an armamentarium of inflammatory genes was positioned in a transcriptionally passive environment suppressing premature transcriptional activation. Upon microbial exposure, however, human neutrophils rapidly (<3 h) repositioned the ensemble of proinflammatory genes toward the transcriptionally permissive compartment. We show that the repositioning of genes was closely associated with the swift recruitment of cohesin across the inflammatory enhancer landscape, permitting an immediate transcriptional response upon bacterial exposure. We found that activated enhancers, marked by increased deposition of H3K27Ac, were highly enriched for cistromic elements associated with PU.1, CEBPB, TFE3, JUN, and FOSL2 occupancy. These data reveal how upon microbial challenge the cohesin machinery is recruited to an activated enhancer repertoire to instruct changes in chromatin folding, nuclear architecture, and to activate an inflammatory gene program.