A1 Refereed original research article in a scientific journal

Vimentin-ERK Signaling Uncouples Slug Gene Regulatory Function




AuthorsVirtakoivu 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

PublisherAMER ASSOC CANCER RESEARCH

Publication year2015

JournalCancer Research

Journal name in sourceCANCER RESEARCH

Journal acronymCANCER RES

Volume75

Issue11

First page 2349

Last page2362

Number of pages14

ISSN0008-5472

eISSN1538-7445

DOIhttps://doi.org/10.1158/0008-5472.CAN-14-2842(external)


Abstract

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.




Last updated on 2024-26-11 at 22:34