title: Control of MT1-MMP transport by atypical PKC during breast-cancer progression.
abstract: 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.
authors.affiliation: Research Center, Institut Curie, 75005 Paris, France.
authors.forename: Carine
authors.initials: C
authors.lastname: Rossé
authors.forename: Catalina
authors.initials: C
authors.lastname: Lodillinsky
authors.forename: Laetitia
authors.initials: L
authors.lastname: Fuhrmann
authors.forename: Maya
authors.initials: M
authors.lastname: Nourieh
authors.forename: Pedro
authors.initials: P
authors.lastname: Monteiro
authors.forename: Marie
authors.initials: M
authors.lastname: Irondelle
authors.forename: Emilie
authors.initials: E
authors.lastname: Lagoutte
authors.forename: Sophie
authors.initials: S
authors.lastname: Vacher
authors.forename: François
authors.initials: F
authors.lastname: Waharte
authors.forename: Perrine
authors.initials: P
authors.lastname: Paul-Gilloteaux
authors.forename: Maryse
authors.initials: M
authors.lastname: Romao
authors.forename: Lucie
authors.initials: L
authors.lastname: Sengmanivong
authors.forename: Mark
authors.initials: M
authors.lastname: Linch
authors.forename: Johan
authors.initials: J
authors.lastname: van Lint
authors.forename: Graça
authors.initials: G
authors.lastname: Raposo
authors.forename: Anne
authors.initials: A
authors.lastname: Vincent-Salomon
authors.forename: Ivan
authors.initials: I
authors.lastname: Bièche
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Parker
authors.forename: Philippe
authors.initials: P
authors.lastname: Chavrier
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D001693:Biological Transport, Active; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D051356:Cortactin / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism; D018450:Disease Progression; D034285:Dynamin II / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D053511:Matrix Metalloproteinase 14 / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015854:Up-Regulation; D000099293:Protein Kinase C-lambda; D000099221:Protein Kinase C zeta
chemical_list: D051356:Cortactin; D034285:Dynamin II; D007527:Isoenzymes; D053511:Matrix Metalloproteinase 14; D011493:Protein Kinase C; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering; D000099293:Protein Kinase C-lambda; D000099221:Protein Kinase C zeta; C495868:CTTN protein, human; C507086:MMP14 protein, human
keywords: MMP14; actin cytoskeleton; membrane traffic; multi-vesicular body
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