Abstract
Type I collagen, the major components of breast interstitial stroma, is able to regulate breast carcinoma cell behavior. Discoidin domain receptor 1 (DDR1) is a type I collagen receptor playing a key role in this process. In fact, collagen/DDR1 axis is able to trigger the downregulation of cell proliferation and the activation of BIK-mediated apoptosis pathway. The aim of this review is to discuss the role of two important factors that regulate these processes. The first factor is the level of DDR1 expression. DDR1 is highly expressed in epithelial-like breast carcinoma cells, but poorly in basal-like ones. Moreover, DDR1 undergoes cleavage by MT1-MMP, which is highly expressed in basal-like breast carcinoma cells. The second factor is type I collagen remodeling since DDR1 activation depends on its fibrillar organization. Collagen remodeling is involved in the regulation of cell proliferation and apoptosis through age- and proteolysis-related modifications.
Highlights
Reviewed by: Marcel Deckert, INSERM U1065 Centre Méditerranéen de Médecine Moléculaire, France Audrey Sirvent, UMR5237 Centre de Recherche en Biologie Cellulaire de Montpellier (CRBM), France
Discoidin domain receptor 1 (DDR1) undergoes cleavage by MT1-MMP, which is highly expressed in basal-like breast carcinoma cells
Our results showed that COL1 aging promotes cell growth by impairing the DDR1/ BIK signaling pathway that induced apoptosis in MCF-7 and ZR-75-1 cells
Summary
Reviewed by: Marcel Deckert, INSERM U1065 Centre Méditerranéen de Médecine Moléculaire, France Audrey Sirvent, UMR5237 Centre de Recherche en Biologie Cellulaire de Montpellier (CRBM), France. DDR1 silencing or interfering with its tyrosine kinase activity by using pharmacological inhibitors prevented the induction the BIK-dependent apoptotic process in the luminal-like cell lines (Assent et al, 2015; Saby et al, 2018), supporting a critical role for DDR1 in 3D COL1-induced apoptosis.
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