Journal
ONCOGENE
Volume 31, Issue 4, Pages 480-493Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2011.249
Keywords
breast cancer; MT1-MMP; apoptosis; type I collagen; BIK
Funding
- MICROENVIMET [FP7-HEALTH-2007-A, 201279]
- Fonds de la Recherche Scientifique Medicale
- Fonds de la Recherche Scientifique - FNRS (FRS-FNRS, Belgium)
- Foundation against Cancer (foundation of public interest, Belgium)
- CGRI-FNRS-INSERM Cooperation
- Fonds speciaux de la Recherche (University of Liege)
- Centre Anticancereux pres l'Universite de Liege
- Fonds Leon Fredericq (University of Liege)
- Direction Generale Operationnelle de l'Economie
- SPW (Region Wallonne, Belgium)
- Fonds Social Europeen (FSE, Belgium)
- Fonds d'Investissements de la Recherche Scientifique (FIRS, CHU Liege, Belgium)
- Belgian Science Policy (Brussels, Belgium)
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As invading breast carcinoma cells breach their underlying basement membrane, they become confronted with a dense three-dimensional reactive stroma dominated by type I collagen. To develop metastatic capabilities, invading tumor cells must acquire the capacity to negotiate this novel microenvironment. Collagen influences the fate of epithelial cells by inducing apoptosis. However, the mechanisms used by invading tumor cells to evade collagen-induced apoptosis remain to be defined. We demonstrate that membrane type-1 matrix metalloproteinase (MT1-MMP/MMP-14) confers breast cancer cells with the ability to escape apoptosis when embedded in a collagen gel and after orthotopic implantation in vivo. In the absence of MMP-14-dependent proteolysis, type I collagen triggers apoptosis by inducing the expression of the pro-apoptotic Bcl-2-interacting killer in luminal-like breast cancer cells. These findings reveal a new mechanism whereby MMP-14 activity promotes tumor progression by circumventing apoptosis. Oncogene (2012) 31, 480-493; doi: 10.1038/onc.2011.249; published online 27 June 2011
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