A1 Refereed original research article in a scientific journal
Vimentin-ERK Signaling Uncouples Slug Gene Regulatory Function
Authors: Virtakoivu R, Mai A, Mattila E, De Franceschi N, Imanishi SY, Corthals G, Kaukonen R, Saari M, Cheng F, Torvaldson E, Kosma VM, Mannermaa A, Muharram G, Gilles C, Eriksson J, Soini Y, Lorens JB, Ivaska J
Publisher: AMER ASSOC CANCER RESEARCH
Publication year: 2015
Journal: Cancer Research
Journal name in source: CANCER RESEARCH
Journal acronym: CANCER RES
Volume: 75
Issue: 11
First page : 2349
Last page: 2362
Number of pages: 14
ISSN: 0008-5472
eISSN: 1538-7445
DOI: https://doi.org/10.1158/0008-5472.CAN-14-2842(external)
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 Slugphosphorylation in EMT initiation. Together, these findings identified a pivotal step in controlling the ability of Slug to organize hallmarks of EMT. (C)2015 AACR.