@article{11b08bcfe4a8410caeb07eda23052e34,
title = "Highly metastatic claudin-low mammary cancers can originate from luminal epithelial cells",
abstract = "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.",
author = "R{\"a}dler, {Patrick D.} and Wehde, {Barbara L.} and Triplett, {Aleata A.} and Hridaya Shrestha and Shepherd, {Jonathan H.} and Pfefferle, {Adam D.} and Hallgeir Rui and Cardiff, {Robert D.} and Perou, {Charles M.} and Wagner, {Kay Uwe}",
note = "Funding Information: The authors thank Kerry Vistisen and Yong Li for animal maintenance and genotyping. We are grateful to Melissa Anders-DiPonio and members of the Animal Model and Therapeutics Evaluation Core Facility at the Karmanos Cancer Institute (KCI) for the preparation of histologic sections. Histologic services were also provided by the KCI Biobanking and Correlative Sciences Core Facility. Dr. Jessica Back, co-director of the KCI Microscopic Imaging and Cytometry Resources Core Facility, assisted in the acquisition and presentation of the flow cytometry data. The KCI core facilities are supported by the Public Health Service grant CA022453. The mammary cancer tran-scriptome analysis was funded, in part, by the METAvivor Research Foundation. Financial support by Public Health Service grants CA117930 and CA202917 (to K.-U. W.) was imperative to maintain selected mutant mouse strains that were used in this study. B.L.W. and P.D.R. received graduate fellowships through the Cancer Research Training Program of the University of Nebraska Medical Center (CA009476). C.M.P. was supported by the Public Health Service grants CA14876 (R01) and CA58223 (P50, NCI Breast SPORE), as well as a grant from the Breast Cancer Research Foundation. J.S. was partially supported by NCI F32CA228326. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: {\textcopyright} 2021, The Author(s).",
year = "2021",
month = dec,
doi = "10.1038/s41467-021-23957-5",
language = "English (US)",
volume = "12",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}