What is it about?

Continuous TAZ activation by deletion of Mob1a/b in mouse mammary luminal epithelium induced rapid mammary tumorigenesis that was dependent on TAZ but not YAP1. Luminal carcinoma in situ developed in mutant animals by 2 wk of age, that later become basal-like breast cancer (BLBC) In a human estrogen receptor+ luminal breast cancer cell line, TAZ hyperactivation skewed the features of these luminal cells to the basal phenotype, consistent with the aberrant TAZ activation frequently observed in human precancerous BLBC lesions. The most frequently mutated gene in human invasive BLBCs is TP53. We found TP53 mutation is rare in human precancerous BLBC. Addition of Trp53 deficiency to our Mob1a/b-deficient mouse model enhanced tumor grade and accelerated cancer progression.

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Why is it important?

Basal-like breast cancer (BLBC) is the most aggressive form of this disease, and patients have a poor prognosis. A universal oncogenic driver of BLBC has resisted identification. Here, we present data suggesting that the Hippo–TAZ pathway is a key driver of BLBC onset and progression.

Perspectives

Our work justifies targeting the Hippo-TAZ pathway as a therapy for human basal-like breast cancer (BLBC) and our mouse model represents a powerful tool for evaluating candidate agents.

Akira Suzuki

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This page is a summary of: Hippo-TAZ signaling is the master regulator of the onset of triple-negative basal-like breast cancers, Proceedings of the National Academy of Sciences, July 2022, Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.2123134119.
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