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

ABSTRACT: Basal breast cancers, an aggressive breast cancer subtype that has poor treatment options, are thought to arise from luminal mammary epithelial cells that undergo basal-like 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 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. Notably, transcriptional analyses of LATS1/2-deleted mammary epithelial cells revealed a gene expression program that associates with human basal 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 breast cancers.

ORGANISM(S): Mus musculus

PROVIDER: GSE196555 | GEO | 2022/09/26

REPOSITORIES: GEO

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

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