DDR1 and MT1-MMP Expression Levels Are Determinant for Triggering BIK-Mediated Apoptosis by 3D Type I Collagen Matrix in Invasive Basal-Like Breast Carcinoma Cells

In conclusion, and in agreement with the other studies (Ford et al., 2007; Koh et al., 2015; Toy et al., 2015; Takai et al., 2018), our data suggest that during the acquisition of mesenchymal features, the level of full-length DDR1 expression should be considered, in addition to the other markers, as an important biomarker in the prognosis of aggressive breast carcinomas. As summarized in Figure 9, the regulation of cell proliferation and apoptosis by the collagen/DDR1 axis involves a differential activation of DDR1 signaling pathway and thus BIK expression. In the case of the basal-like breast carcinoma cells, collagen proteolysis by MT1-MMP, the low expression of DDR1, and its cleavage by MT1-MMP could contribute to cell survival in the interstitial microenvironment. However, although our in vitro data suggest that low level of DDR1 expression should be considered as an additional important biomarker in the prognosis of breast carcinoma, these data need to be confirmed in future animal studies. FIGURE 9 Figure 9. Proposed model highlighting the importance of MT1-MMP and DDR1 expression balance in the regulation of cell growth and survival in breast cancer cells cultivated in 3D type I collagen matrix. Finally, it is important to keep in mind that despite its low expression level in the aggressive breast carcinomas, DDR1 plays also a crucial role in the proteolysis-based cell invasion of a collagen-rich stroma (Juin et al., 2014)...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research