Journal
EMBO REPORTS
Volume 17, Issue 2, Pages 188-201Publisher
WILEY
DOI: 10.15252/embr.201540488
Keywords
gene expression; metabolism; mutant p53 and YAP; proliferation; statin
Categories
Funding
- Italian Association for Cancer Research (AIRC) Special Program Molecular Clinical Oncology 5 per mille [10016]
- Italian Ministry of Health
- Italian Association for Cancer Research (AIRC) [14455]
- Epigenomics Flagship Project (EPIGEN)
- Cancer Research UK
- British Columbia Cancer Agency Branch
Ask authors/readers for more resources
Mutant p53 proteins are present in more than half of human cancers. Yes-associated protein (YAP) is a key transcriptional regulator controlling organ growth, tissue homeostasis, and cancer. Here, we report that these two determinants of human malignancy share common transcriptional signatures. YAP physically interacts with mutant p53 proteins in breast cancer cells and potentiates their pro-proliferative transcriptional activity. We found YAP as well as mutant p53 and the transcription factor NF-Y onto the regulatory regions of cyclin A, cyclin B, and CDK1 genes. Either mutant p53 or YAP depletion down-regulates cyclin A, cyclin B, and CDK1 gene expression and markedly slows the growth of diverse breast cancer cell lines. Pharmacologically induced cytoplasmic re-localization of YAP reduces the expression levels of cyclin A, cyclin B, and CDK1 genes both in vitro and in vivo. Interestingly, primary breast cancers carrying p53 mutations and displaying high YAP activity exhibit higher expression levels of cyclin A, cyclin B, and CDK1 genes when compared to wt-p53 tumors.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available