| First Author | Takai K | Year | 2018 |
| Journal | Genes Dev | Volume | 32 |
| Issue | 3-4 | Pages | 244-257 |
| PubMed ID | 29483153 | Mgi Jnum | J:272436 |
| Mgi Id | MGI:6284936 | Doi | 10.1101/gad.301366.117 |
| Citation | Takai K, et al. (2018) Discoidin domain receptor 1 (DDR1) ablation promotes tissue fibrosis and hypoxia to induce aggressive basal-like breast cancers. Genes Dev 32(3-4):244-257 |
| abstractText | The discoidin domain receptor 1 (DDR1) is overexpressed in breast carcinoma cells. Low DDR1 expression is associated with worse relapse-free survival, reflecting its controversial role in cancer progression. We detected DDR1 on luminal cells but not on myoepithelial cells of DDR1(+/+) mice. We found that DDR1 loss compromises cell adhesion, consistent with data that older DDR1(-/-) mammary glands had more basal/myoepithelial cells. Basal cells isolated from older mice exerted higher traction forces than the luminal cells, in agreement with increased mammary branches observed in older DDR1(-/-) mice and higher branching by their isolated organoids. When we crossed DDR1(-/-) mice with MMTV-PyMT mice, the PyMT/DDR1(-/-) mammary tumors grew faster and had increased epithelial tension and matricellular fibrosis with a more basal phenotype and increased lung metastases. DDR1 deletion induced basal differentiation of CD90(+)CD24(+) cancer cells, and the increase in basal cells correlated with tumor cell mitoses. K14(+) basal cells, including K8(+)K14(+) cells, were increased adjacent to necrotic fields. These data suggest that the absence of DDR1 provides a growth and adhesion advantage that favors the expansion of basal cells, potentiates fibrosis, and enhances necrosis/hypoxia and basal differentiation of transformed cells to increase their aggression and metastatic potential. |
