| First Author | Rädler PD | Year | 2021 |
| Journal | Nat Commun | Volume | 12 |
| Issue | 1 | Pages | 3742 |
| PubMed ID | 34145248 | Mgi Jnum | J:307916 |
| Mgi Id | MGI:6725494 | Doi | 10.1038/s41467-021-23957-5 |
| Citation | Radler PD, et al. (2021) Highly metastatic claudin-low mammary cancers can originate from luminal epithelial cells. Nat Commun 12(1):3742 |
| abstractText | Claudin-low breast cancer represents an aggressive molecular subtype that is comprised of mostly triple-negative mammary tumor cells that possess stem cell-like and mesenchymal features. Little is known about the cellular origin and oncogenic drivers that promote claudin-low breast cancer. In this study, we show that persistent oncogenic RAS signaling causes highly metastatic triple-negative mammary tumors in mice. More importantly, the activation of endogenous mutant KRAS and expression of exogenous KRAS specifically in luminal epithelial cells in a continuous and differentiation stage-independent manner induces preneoplastic lesions that evolve into basal-like and claudin-low mammary cancers. Further investigations demonstrate that the continuous signaling of oncogenic RAS, as well as regulators of EMT, play a crucial role in the cellular plasticity and maintenance of the mesenchymal and stem cell characteristics of claudin-low mammary cancer cells. |
