Publication Date
7-19-2022
Journal
Proceedings of the National Academy of Sciences of the United States of America
DOI
10.1073/pnas.2123134119
PMID
35858357
PMCID
PMC9303858
PubMedCentral® Posted Date
7-11-2022
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Adaptor Proteins, Signal Transducing, Animals, Carcinogenesis, Cell Line, Tumor, Female, Gene Deletion, Hippo Signaling Pathway, Humans, Intracellular Signaling Peptides and Proteins, Mammary Neoplasms, Experimental, Mice, Precancerous Conditions, Receptors, Estrogen, Transcriptional Coactivator with PDZ-Binding Motif Proteins, Triple Negative Breast Neoplasms, Tumor Suppressor Protein p53, YAP-Signaling Proteins, MOB1, TAZ, Hippo, triple-negative breast cancer, basal-like breast cancer
Abstract
A universal oncogenic driver of basal-like breast cancer (BLBC) has resisted identification. We show that continuous transcriptional coactivator with PDZ-binding motif (TAZ) activation in precancerous murine luminal cells generates luminal cancers that later become BLBCs. Subsequent TP53 alteration, a feature of invasive human BLBCs, accelerates tumor progression. Because BLBC development is inhibited by TAZ inactivation in vivo, our work provides a sound rationale for targeting Hippo-TAZ signaling as therapy for human BLBC. Our mouse model of BLBC represents a powerful tool for evaluating such drugs.
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