| First Author | Tornillo G | Year | 2018 |
| Journal | Cell Rep | Volume | 25 |
| Issue | 13 | Pages | 3674-3692.e10 |
| PubMed ID | 30590041 | Mgi Jnum | J:270746 |
| Mgi Id | MGI:6278681 | Doi | 10.1016/j.celrep.2018.11.103 |
| Citation | Tornillo G, et al. (2018) Dual Mechanisms of LYN Kinase Dysregulation Drive Aggressive Behavior in Breast Cancer Cells. Cell Rep 25(13):3674-3692.e10 |
| abstractText | The SRC-family kinase LYN is highly expressed in triple-negative/basal-like breast cancer (TNBC) and in the cell of origin of these tumors, c-KIT-positive luminal progenitors. Here, we demonstrate LYN is a downstream effector of c-KIT in normal mammary cells and protective of apoptosis upon genotoxic stress. LYN activity is modulated by PIN1, a prolyl isomerase, and in BRCA1 mutant TNBC PIN1 upregulation activates LYN independently of c-KIT. Furthermore, the full-length LYN splice isoform (as opposed to the Deltaaa25-45 variant) drives migration and invasion of aggressive TNBC cells, while the ratio of splice variants is informative for breast cancer-specific survival across all breast cancers. Thus, dual mechanisms-uncoupling from upstream signals and splice isoform ratios-drive the activity of LYN in aggressive breast cancers. |
