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| Status |
Public on Sep 26, 2022 |
| Title |
Inactivation of LATS1/2 drives luminal-basal plasticity to initiate basal-like mammary carcinomas |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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.
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| Overall design |
Lineage-traced mammary cells from control (lsl-EYFP; K8CreERT2), LATS1/2-KO (LATS1/2f/f; lsl-EYFP; K8CreERT2), and LATS1/2-Sox9-KO (LATS1/2f/f; Sox9f/f; lsl-EYFP; K8CreERT2) mice were isolated and transcriptionally profiled. Each condition had three replicates.
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| Contributor(s) |
Kern J, Varelas X |
| Citation(s) |
36443313 |
| Submission date |
Feb 11, 2022 |
| Last update date |
Nov 29, 2022 |
| Contact name |
Boting Ning |
| E-mail(s) |
ningb@bu.edu
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| Organization name |
BOSTON UNIVERSITY
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| Street address |
72 E Concord St
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| City |
BOSTON |
| State/province |
Massachusetts |
| ZIP/Postal code |
02118 |
| Country |
USA |
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| Platforms (1) |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA805501 |
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