MT1-MMP proinvasive activity is regulated by a novel Rab8-dependent exocytic pathway

Jose J. Bravo-Cordero, Raquel Marrero-Diaz, Diego Megías, Laura Genís, Aranzazu García-Grande, Maria A. García, Alicia G. Arroyo, María C. Montoya

Research output: Contribution to journalArticle

163 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1499-1510
Number of pages12
JournalEMBO Journal
Volume26
Issue number6
DOIs
StatePublished - Mar 21 2007
Externally publishedYes

Fingerprint

Matrix Metalloproteinase 14
Tumors
Collagen
Cells
GTP Phosphohydrolases
Exocytosis
Collagen Type I
Integrins
Machinery
Cell Movement
Neoplasms
Adenocarcinoma
Peptide Hydrolases
Adhesion
Degradation

Keywords

  • Matrix metalloproteinases
  • Membrane traffic
  • MT1-MMP
  • Rab8
  • Tumor invasion

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Bravo-Cordero, J. J., Marrero-Diaz, R., Megías, D., Genís, L., García-Grande, A., García, M. A., ... Montoya, M. C. (2007). MT1-MMP proinvasive activity is regulated by a novel Rab8-dependent exocytic pathway. EMBO Journal, 26(6), 1499-1510. https://doi.org/10.1038/sj.emboj.7601606

MT1-MMP proinvasive activity is regulated by a novel Rab8-dependent exocytic pathway. / Bravo-Cordero, Jose J.; Marrero-Diaz, Raquel; Megías, Diego; Genís, Laura; García-Grande, Aranzazu; García, Maria A.; Arroyo, Alicia G.; Montoya, María C.

In: EMBO Journal, Vol. 26, No. 6, 21.03.2007, p. 1499-1510.

Research output: Contribution to journalArticle

Bravo-Cordero, JJ, Marrero-Diaz, R, Megías, D, Genís, L, García-Grande, A, García, MA, Arroyo, AG & Montoya, MC 2007, 'MT1-MMP proinvasive activity is regulated by a novel Rab8-dependent exocytic pathway', EMBO Journal, vol. 26, no. 6, pp. 1499-1510. https://doi.org/10.1038/sj.emboj.7601606
Bravo-Cordero JJ, Marrero-Diaz R, Megías D, Genís L, García-Grande A, García MA et al. MT1-MMP proinvasive activity is regulated by a novel Rab8-dependent exocytic pathway. EMBO Journal. 2007 Mar 21;26(6):1499-1510. https://doi.org/10.1038/sj.emboj.7601606
Bravo-Cordero, Jose J. ; Marrero-Diaz, Raquel ; Megías, Diego ; Genís, Laura ; García-Grande, Aranzazu ; García, Maria A. ; Arroyo, Alicia G. ; Montoya, María C. / MT1-MMP proinvasive activity is regulated by a novel Rab8-dependent exocytic pathway. In: EMBO Journal. 2007 ; Vol. 26, No. 6. pp. 1499-1510.
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