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 language | English (US) |
|---|---|
| Pages (from-to) | 1499-1510 |
| Number of pages | 12 |
| Journal | EMBO Journal |
| Volume | 26 |
| Issue number | 6 |
| DOIs | |
| State | Published - Mar 21 2007 |
| Externally published | Yes |
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Keywords
- Matrix metalloproteinases
- Membrane traffic
- MT1-MMP
- Rab8
- Tumor invasion
ASJC Scopus subject areas
- Genetics
- Cell Biology
Cite this
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 journal › Article
}
TY - JOUR
T1 - MT1-MMP proinvasive activity is regulated by a novel Rab8-dependent exocytic pathway
AU - Bravo-Cordero, Jose J.
AU - Marrero-Diaz, Raquel
AU - Megías, Diego
AU - Genís, Laura
AU - García-Grande, Aranzazu
AU - García, Maria A.
AU - Arroyo, Alicia G.
AU - Montoya, María C.
PY - 2007/3/21
Y1 - 2007/3/21
N2 - 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.
AB - 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.
KW - Matrix metalloproteinases
KW - Membrane traffic
KW - MT1-MMP
KW - Rab8
KW - Tumor invasion
UR - http://www.scopus.com/inward/record.url?scp=33947597433&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33947597433&partnerID=8YFLogxK
U2 - 10.1038/sj.emboj.7601606
DO - 10.1038/sj.emboj.7601606
M3 - Article
VL - 26
SP - 1499
EP - 1510
JO - EMBO Journal
JF - EMBO Journal
SN - 0261-4189
IS - 6
ER -