Journal
CELL CYCLE
Volume 14, Issue 1, Pages 146-156Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/15384101.2014.967106
Keywords
Hippo pathway; TAZ; breast cancer; cancer stem cells; mammary tumorigenesis
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Funding
- Roswell Park Cancer Institute
- National Cancer Institute (NCI) [P30 CA016056, R21 CA179693]
- American Cancer Society Institutional Research Grant [02-197-04]
- NATIONAL CANCER INSTITUTE [R01CA172115, R01CA131231, P30CA016056, R01CA106768, R21CA179693] Funding Source: NIH RePORTER
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The Hippo pathway is an evolutionarily conserved regulator of tissue growth and cell fate during development and regeneration. Conversely, deregulation of the Hippo pathway has been reported in several malignancies. Here, we used integrative functional genomics approaches to identify TAZ, a transcription co-activator and key downstream effector of the Hippo pathway, as an essential driver for the propagation of TNBC malignant phenotype. We further showed in non-transformed human mammary basal epithelial cells that expression of constitutively active TAZ confers cancer stem cell (CSC) traits that are dependent on the TAZ and TEAD interacting domains. In addition, to gain a better understanding of how TAZ functions, we performed genetic-function analysis of TAZ. Significantly, we identified that both the WW and transcriptional activation domains of TAZ are critical for the induced CSC properties as well as tumorigenic potential as manifested in vitro and in human breast cancer xenograft in vivo. Collectively, our data suggest that pharmacological inhibition of TAZ activity may provide a novel means of targeting and eliminating breast CSCs.
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