Inactivation of LATS1/2 drives luminal-basal plasticity to initiate basal-like mammary carcinomas

Joseph G. Kern, Andrew M. Tilston-Lunel, Anthony Federico, Boting Ning, Amy Mueller, Grace B. Peppler, Eleni Stampouloglou, Nan Cheng, Randy L. Johnson, Marc E. Lenburg, Jennifer E. Beane, Stefano Monti and Xaralabos Varelas ()
Additional contact information
Joseph G. Kern: Boston University School of Medicine
Andrew M. Tilston-Lunel: Boston University School of Medicine
Anthony Federico: Boston University School of Medicine
Boting Ning: Boston University School of Medicine
Amy Mueller: Boston University School of Medicine
Grace B. Peppler: Boston University School of Medicine
Eleni Stampouloglou: Boston University School of Medicine
Nan Cheng: Boston University School of Medicine
Randy L. Johnson: MD Anderson Cancer Center
Marc E. Lenburg: Boston University School of Medicine
Jennifer E. Beane: Boston University School of Medicine
Stefano Monti: Boston University School of Medicine
Xaralabos Varelas: Boston University School of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract Basal-like breast cancers, an aggressive breast cancer subtype that has poor treatment options, are thought to arise from luminal mammary epithelial cells that undergo basal plasticity through poorly understood mechanisms. Using genetic mouse models and ex vivo primary organoid cultures, we show that conditional co-deletion of the LATS1 and LATS2 kinases, key effectors of Hippo pathway signaling, in mature mammary luminal epithelial cells promotes the development of Krt14 and Sox9-expressing basal-like carcinomas that metastasize over time. Genetic co-deletion experiments revealed that phenotypes resulting from the loss of LATS1/2 activity are dependent on the transcriptional regulators YAP/TAZ. Gene expression analyses of LATS1/2-deleted mammary epithelial cells notably revealed a transcriptional program that associates with human basal-like breast cancers. Our study demonstrates in vivo roles for the LATS1/2 kinases in mammary epithelial homeostasis and luminal-basal fate control and implicates signaling networks induced upon the loss of LATS1/2 activity in the development of basal-like breast cancer.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-34864-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34864-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-34864-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().