期刊
CANCER RESEARCH
卷 75, 期 11, 页码 2349-2362出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-14-2842
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资金
- Academy of Finland
- ERC [202809, 615258]
- Sigrid Juselius Foundation
- Finnish Cancer Organization
- K. Albin Johansson Foundation
- Lounais-Suomen syopayhdistys
- Instrumentariumin tiedesaatio
- Orion Research Foundation
- Turku Doctoral Program of Biomedical Sciences
- Drug Research Doctoral Program
- Academy of Finland postdoc grant
- European Research Council (ERC) [615258, 202809] Funding Source: European Research Council (ERC)
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.
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