Control of MT1-MMP transport by atypical PKC during breast-cancer progression

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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 | Chavrier, Philippe | Rosse, C. | Bieche, I.

Edité par CCSD ; National Academy of Sciences -

International audience. 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 endosomes and regulates cortactin association with the membrane scission protein dynamin-2. Thus, cell line-based observations and clinical data reveal the concerted activity of aPKC, cortactin, and dynamin-2, which control the trafficking of MT1-MMP from late endosome to the plasma membrane and play an important role in the invasive potential of breast-cancer cells.

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