Vimentin-ERK Signaling Uncouples Slug Gene Regulatory Function.
; ; et al
in Cancer research (2015), 75(11), 2349-62
Epithelial-mesenchymal transition (EMT) in cells is a developmental process adopted during tumorigenesis that promotes metastatic capacity. In this study, we advance understanding of EMT control in cancer ... [more ▼]
Epithelial-mesenchymal transition (EMT) in cells is a developmental process adopted during tumorigenesis that promotes metastatic capacity. In this study, we advance understanding of EMT control in cancer cells with the description of a novel vimentin-ERK axis that regulates the transcriptional activity of Slug (SNAI2). Vimentin, ERK, and Slug exhibited overlapping subcellular localization in clinical specimens of triple-negative breast carcinoma. RNAi-mediated ablation of these gene products inhibited cancer cell migration and cell invasion through a laminin-rich matrix. Biochemical analyses demonstrated direct interaction of vimentin and ERK, which promoted ERK activation and enhanced vimentin transcription. Consistent with its role as an intermediate filament, vimentin acted as a scaffold to recruit Slug to ERK and promote Slug phosphorylation at serine-87. Site-directed mutagenesis established a requirement for ERK-mediated Slug phosphorylation in EMT initiation. Together, these findings identified a pivotal step in controlling the ability of Slug to organize hallmarks of EMT. [less ▲]Detailed reference viewed: 23 (0 ULg)
Robustness of car parks against localised fire - Deliverable I: Definition of the problem and selection of the appropriate investigation ways
Jaspart, Jean-Pierre ; Demonceau, Jean-François ; et al
Grant Agreement Number RFSR-CT-2008-00036Detailed reference viewed: 44 (4 ULg)