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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 111; no. 18; pp. E1872 - E1879
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 06.05.2014; National Acad Sciences
• Series: PNAS Plus
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Adult; Aged; Biological Sciences; Biological Transport, Active; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Carcinoma, Ductal, Breast - genetics; Carcinoma, Ductal, Breast - metabolism; Carcinoma, Ductal, Breast - pathology; Cell Line, Tumor; Cells; Cortactin - metabolism; Cytoplasmic Granules - metabolism; Disease Progression; Dynamin II - metabolism; Endosomes - metabolism; Enzymes; Extracellular Matrix - metabolism; Female; Humans; Isoenzymes - antagonists & inhibitors; Isoenzymes - genetics; Isoenzymes - metabolism; Kinases; Life Sciences; Matrix Metalloproteinase 14 - genetics; Matrix Metalloproteinase 14 - metabolism; Metastasis; Middle Aged; Neoplasm Invasiveness; Phosphorylation; PNAS Plus; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - genetics; Protein Kinase C - metabolism; RNA Interference; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Neoplasm - genetics; RNA, Neoplasm - metabolism; RNA, Small Interfering - genetics; T cell receptors; Tumors; Up-Regulation; actin cytoskeleton; MMP14; multi-vesicular body; membrane traffic
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1400749111

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.