biostudies-literatureKern JGAmerican Cancer SocietyNIDCR NIH HHSU.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial ResearchNHLBI NIH HHSU.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood InstituteNCI NIH HHSU.S. Department of Health & Human Services | NIH | NCI | Division of Cancer Epidemiology and Genetics, National Cancer Institute7198https://www.ebi.ac.uk/biostudies/studies/S-EPMC9705439biostudies-literatureUnknown13(1)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 transcrNature communicationsInactivation of LATS1/2 drives luminal-basal plasticity to initiate basal-like mammary carcinomas.PMC9705439R01DE031831F31 CA232683R01 HL124392R01HL124392R01 DE031831RSG- 17-138-01-CSMF31CA232683R01DE030350R01 DE030350Kern JGNing BBeane JEPeppler GBStampouloglou EJohnson RLMueller ALenburg MEVarelas XTilston-Lunel AMFederico AMonti SCheng NfalseInactivation of LATS1/2 drives luminal-basal plasticity to initiate basal-like mammary carcinomas.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 transcr2022-01-01T00:00:00Z2022 Nov2026-05-29T04:34:32.712Z2025-04-06T14:07:39.014ZS-EPMC97054393644331310.1038/s41467-022-34864-8