| First Author | Engelsen AST | Year | 2020 |
| Journal | iScience | Volume | 23 |
| Issue | 11 | Pages | 101649 |
| PubMed ID | 33103086 | Mgi Jnum | J:307248 |
| Mgi Id | MGI:6717550 | Doi | 10.1016/j.isci.2020.101649 |
| Citation | Engelsen AST, et al. (2020) AXL Is a Driver of Stemness in Normal Mammary Gland and Breast Cancer. iScience 23(11):101649 |
| abstractText | The receptor tyrosine kinase AXL is associated with epithelial plasticity in several solid tumors including breast cancer and AXL-targeting agents are currently in clinical trials. We hypothesized that AXL is a driver of stemness traits in cancer by co-option of a regulatory function normally reserved for stem cells. AXL-expressing cells in human mammary epithelial ducts co-expressed markers associated with multipotency, and AXL inhibition abolished colony formation and self-maintenance activities while promoting terminal differentiation in vitro. Axl-null mice did not exhibit a strong developmental phenotype, but enrichment of Axl (+) cells was required for mouse mammary gland reconstitution upon transplantation, and Axl-null mice had reduced incidence of Wnt1-driven mammary tumors. An AXL-dependent gene signature is a feature of transcriptomes in basal breast cancers and reduced patient survival irrespective of subtype. Our interpretation is that AXL regulates access to epithelial plasticity programs in MaSCs and, when co-opted, maintains acquired stemness in breast cancer cells. |
