Control of MT1-MMP transport by atypical PKC during breast-cancer progression
- Rossé, Carine
- Lodillinsky, Catalina
- Fuhrmann, Laetitia
- Nourieh, Maya
- Monteiro, Pedro
- Irondelle, Marie
- Lagoutte, Emilie
- Vacher, Sophie
- Waharte, François
- Paul Gilloteaux, Perrine
- Romao, Maryse
- Sengmanivong, Lucie
- Linch, Mark
- Van Lint, Johan
- Raposo, Graça
- Vincent Salomon, Anne
- Bièche, Ivan
- Parker, Peter J.
- Chavrier, Philippe
DOIAbstract
Dissemination of carcinoma cells requires the pericellular degradation of the extracellular matrix, which is mediated by membrane type 1-matrix metalloproteinase (MT1-MMP). In this article, we report a co–up-regulation and colocalization of MT1-MMP and atypical protein kinase C iota (aPKCι) in hormone receptor-negative breast tumors in association with a higher risk of metastasis. Silencing of aPKC in invasive breast-tumor cell lines impaired the delivery of MT1-MMP from late endocytic storage compartments to the surface and inhibited matrix degradation and invasion. We provide evidence that aPKCι, in association with MT1-MMP–containing endosomes, phosphorylates cortactin, which is present in F-actin–rich puncta on MT1-MMP–positive endosome...
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