title: MT1-MMP protects breast carcinoma cells against type I collagen-induced apoptosis.
abstract: 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.
authors.affiliation: Laboratory of Tumor and Developmental Biology, GIGA-Cancer, Institute of Pathology, University of Liège, Liège, Belgium. erik.maquoi@ulg.ac.be
authors.forename: E
authors.initials: E
authors.lastname: Maquoi
authors.forename: D
authors.initials: D
authors.lastname: Assent
authors.forename: J
authors.initials: J
authors.lastname: Detilleux
authors.forename: C
authors.initials: C
authors.lastname: Pequeux
authors.forename: J-M
authors.initials: JM
authors.lastname: Foidart
authors.forename: A
authors.initials: A
authors.lastname: Noël
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000502:physiology; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D024042:Collagen Type I / Q000494:pharmacology*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D024101:Mitochondrial Proteins; D009361:Neoplasm Invasiveness
chemical_list: D051017:Apoptosis Regulatory Proteins; C096820:BIK protein, human; D024042:Collagen Type I; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14