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- Title
MT1-MMP proinvasive activity is regulated by a novel Rab8-dependent exocytic pathway.
- Authors
Bravo-Cordero, Jose J.; Marrero-Diaz, Raquel; Megías, Diego; Genís, Laura; García-Grande, Aranzazu; García, Maria A.; Arroyo, Alicia G.; Montoya, María C.
- Abstract
MT1-matrix metalloproteinase (MT1-MMP) is one of the most critical factors in the invasion machinery of tumor cells. Subcellular localization to invasive structures is key for MT1-MMP proinvasive activity. However, the mechanism driving this polarized distribution remains obscure. We now report that polarized exocytosis of MT1-MMP occurs during MDA-MB-231 adenocarcinoma cell migration into collagen type I three-dimensional matrices. Polarized trafficking of MT1-MMP is triggered by β1 integrin-mediated adhesion to collagen, and is required for protease localization at invasive structures. Localization of MT1-MMP within VSV-G/Rab8-positive vesicles, but not in Rab11/Tf/TfRc-positive compartment in invasive cells, suggests the involvement of the exocytic traffic pathway. Furthermore, constitutively active Rab8 mutants induce MT1-MMP exocytic traffic, collagen degradation and invasion, whereas Rab8- but not Rab11-knockdown inhibited these processes. Altogether, these data reveal a novel pathway of MT1-MMP redistribution to invasive structures, exocytic vesicle trafficking, which is crucial for its role in tumor cell invasiveness. Mechanistically, MT1-MMP delivery to invasive structures, and therefore its proinvasive activity, is regulated by Rab8 GTPase.
- Subjects
METALLOPROTEINASES; EXOCYTOSIS; ADENOCARCINOMA; CELL migration; GUANOSINE triphosphatase; COLLAGEN
- Publication
EMBO Journal, 2007, Vol 26, Issue 6, p1499
- ISSN
0261-4189
- Publication type
Article
- DOI
10.1038/sj.emboj.7601606