Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 111, Issue 18, Pages E1872-E1879Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1400749111
Keywords
membrane traffic; actin cytoskeleton; multi-vesicular body; MMP14
Categories
Funding
- Fondation ARC pour la Recherche sur le Cancer (ARC)
- Incentive and Cooperative Research Programme Breast Cancer: Cell Invasion and Motility of Institut Curie
- ARC [SL220100601356]
- Agence Nationale pour la Recherche [ANR-08-BLAN-0111]
- Institut National du Cancer [2012-1-PL BIO-02-IC-1]
- Institut Curie
- Centre National pour la Recherche Scientifique
- French National Research Agency [ANR-10-INSB-04]
- Agence Nationale de la Recherche (ANR) [ANR-08-BLAN-0111] Funding Source: Agence Nationale de la Recherche (ANR)
- Cancer Research UK [15683] Funding Source: researchfish
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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 (aPKC iota) 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 aPKC iota, 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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