AXL Is a Driver of Stemness in Normal Mammary Gland and Breast Cancer
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- AXL Is a Driver of Stemness in Normal Mammary Gland and Breast Cancer
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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.
Originalsprog | Engelsk |
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Artikelnummer | 101649 |
Tidsskrift | iScience |
Vol/bind | 23 |
Udgave nummer | 11 |
Antal sider | 40 |
ISSN | 2589-0042 |
DOI | |
Status | Udgivet - 2020 |
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