| First Author | Xiao Q | Year | 2015 |
| Journal | PLoS Genet | Volume | 11 |
| Issue | 5 | Pages | e1005249 |
| PubMed ID | 25992553 | Mgi Jnum | J:224784 |
| Mgi Id | MGI:5689067 | Doi | 10.1371/journal.pgen.1005249 |
| Citation | Xiao Q, et al. (2015) Minor Type IV Collagen alpha5 Chain Promotes Cancer Progression through Discoidin Domain Receptor-1. PLoS Genet 11(5):e1005249 |
| abstractText | Type IV collagens (Col IV), components of basement membrane, are essential in the maintenance of tissue integrity and proper function. Alteration of Col IV is related to developmental defects and diseases, including cancer. Col IV alpha chains form alpha1alpha1alpha2, alpha3alpha4alpha5 and alpha5alpha5alpha6 protomers that further form collagen networks. Despite knowledge on the functions of major Col IV (alpha1alpha1alpha2), little is known whether minor Col IV (alpha3alpha4alpha5 and alpha5alpha5alpha6) plays a role in cancer. It also remains to be elucidated whether major and minor Col IV are functionally redundant. We show that minor Col IV alpha5 chain is indispensable in cancer development by using alpha5(IV)-deficient mouse model. Ablation of alpha5(IV) significantly impeded the development of KrasG12D-driven lung cancer without affecting major Col IV expression. Epithelial alpha5(IV) supports cancer cell proliferation, while endothelial alpha5(IV) is essential for efficient tumor angiogenesis. alpha5(IV), but not alpha1(IV), ablation impaired expression of non-integrin collagen receptor discoidin domain receptor-1 (DDR1) and downstream ERK activation in lung cancer cells and endothelial cells. Knockdown of DDR1 in lung cancer cells and endothelial cells phenocopied the cells deficient of alpha5(IV). Constitutively active DDR1 or MEK1 rescued the defects of alpha5(IV)-ablated cells. Thus, minor Col IV alpha5(IV) chain supports lung cancer progression via DDR1-mediated cancer cell autonomous and non-autonomous mechanisms. Minor Col IV can not be functionally compensated by abundant major Col IV. |
