Epithelial discoidin domain-containing receptor 1 precursor (EC 2.7.10.1) (Epithelial discoidin domain receptor 1) (CD167 antigen-like family member A) (Cell adhesion kinase) (Discoidin receptor tyrosine kinase) (HGK2) (Mammary carcinoma kinase 10) (MCK-10) (Protein-tyrosine kinase 3A) (Protein-tyrosine kinase RTK-6) (TRK E) (Tyrosine kinase DDR) (Tyrosine-protein kinase CAK) (CD167a antigen) [CAK] [EDDR1] [NEP] [NTRK4] [PTK3A] [RTK6] [TRKE]
развернуть
Age-related modifications of type I collagen impair
DDR1-induced apoptosis in non-invasive breast carcinoma cells.
Type I collagen and DDR1 axis has been described to decrease cell proliferation and to initiate apoptosis in non-invasive breast carcinoma in three-dimensional cell culture matrices. Moreover, MT1-MMP down-regulates these effects. Here, we address the effect of type I collagen aging and MT1-MMP expression on cell proliferation suppression and induced-apoptosis in non-invasive MCF-7 and ZR-75-1 breast carcinoma. We provide evidence for a decrease in cell growth and an increase in apoptosis in the presence of adult collagen when compared to old collagen. This effect involves a differential activation of DDR1, as evidenced by a higher DDR1 phosphorylation level in adult collagen. In adult collagen, inhibition of DDR1 expression and kinase function induced an increase in cell growth to a level similar to that observed in old collagen. The impact of aging on the sensitivity of collagen to MT1-MMP has been reported recently. We used the MT1-MMP expression strategy to verify whether, by degrading adult type I collagen, it could lead to the same phenotype observed in old collagen 3D matrix. MT1-MMP overexpression abrogated the proliferation suppression and induced-apoptosis effects only in the presence of adult collagen. This suggests that differential collagen degradation by MT1-MMP induced a structural disorganization of adult collagen and inhibits DDR1 activation. This could in turn impair DDR1-induced cell growth suppression and apoptosis. Taken together, our data suggest that modifications of collagen structural organization, due to aging, contribute to the loss of the growth suppression and induced apoptosis effect of collagen in luminal breast carcinoma. MT1-MMP-dependent degradation and aging of collagen have no additive effects on these processes.
MeSH Terms
- Aging
- Animals
- Apoptosis
- Apoptosis Regulatory Proteins
- Breast Neoplasms
- Cell Line, Tumor
- Cell Proliferation
- Collagen Type I
- Discoidin Domain Receptor 1
- Female
- Gene Silencing
- Humans
- Matrix Metalloproteinase 14
- Membrane Proteins
- Mitochondrial Proteins
- Neoplasm Invasiveness
- Neoplasm Proteins
- Rats, Wistar
- Up-Regulation
Keywords
- Aging
- Apoptosis
- Breast carcinoma
- DDR1
- Type I collagen