HMG-CoA Reductase Inhibitor Statins Activate the Transcriptional Activity of p53 by Regulating the Expression of TAZ
Open accessAbstract
Transcriptional coactivator with PDZ-binding motif (TAZ) is a downstream transcriptional regulator of the Hippo pathway that controls cell growth and differentiation. The aberrant activation of TAZ correlates with a poor prognosis in human cancers, such as breast and colon cancers. We previously demonstrated that TAZ inhibited the tumor suppressor functions of p53 and enhanced cell proliferation. Statins, which are used to treat dyslipidemia, have been reported to suppress the activity of TAZ and exert anti-tumor effects. In the present study, we focused on the regulation of p53 functions by TAZ and investigated whether statins modulate these functions via TAZ. The results obtained suggest that statins, such as simvastatin and fluvastatin, activated the transcriptional function of p53 by suppressing TAZ protein expression. Furthermore, co-treatment with simvastatin and anti-tumor agents that cooperatively activate p53 suppressed cancer cell survival. These results indicate a useful mechanism by which statins enhance the effects of anti-tumor agents through the activation of p53 and may represent a novel approach to cancer therapy.
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Simvastatin used in combination with nutlin-3 reduces cell viability through suppression of MDM2 and activation of wild-type P53.
“When used in combination with nutlin-3, simvastatin was found to reduce cell viability through the suppression of MDM2 and activation of wild-type P53.133”
From Drug repurposing for cancer therapy (2024) · cites this paper as [133]
Simvastatin and fluvastatin activate the transcriptional function of P53 by suppressing TAZ protein expression.
“Miyajima and colleagues found that simvastatin and fluvastatin activated the transcriptional function of P53 by suppressing TAZ protein expression.”
From Drug repurposing for cancer therapy (2024) · cites this paper as [133]
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BindingDB (2026) · UC San Diego · doi:10.7270/q2z03f0t
- Authors
- Miyajima, C., Hayakawa, Y., Inoue, Y., Nagasaka, M., & Hayashi, H.
- Affiliations
- Nagoya City University (JP)
- Corresponding author
- Inoue, Yasumichi
- Hayashi, Hidetoshi
- Venue
- Pharmaceuticals
- Publisher
- MDPI AG
- Published
- 2022-08-17
- Volume
- 15
- Issue
- 8
- Pages
- 1015
- ISSN
- 1424-8247 (ISSN-L)
- PMC
- PMC9412369
- OpenAlex
- W4292260863
- Cited by
- 17
- References
- 43
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 6 · 2023: 6 · 2022: 1
- FWCI
- 2.14
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Pharmaceuticals (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Grants-in-Aid for Scientific Research (C) (18K06660, 20K07052, 21H02650, 18K16081, 2021103, 2022005, 2221102, JPMJSP213)
- Grant-in-Aid for Scientific Research (B) (18K06660, 20K07052, 21H02650, 18K16081, 2021103, 2022005, 2221102, JPMJSP213)
- Grant-in-Aid for Young Scientists from the Japan Society for the Promotion of Science (JSPS) (18K06660, 20K07052, 21H02650, 18K16081, 2021103, 2022005, 2221102, JPMJSP213)
- Grants-in-Aid for Research from Nagoya City University (18K06660, 20K07052, 21H02650, 18K16081, 2021103, 2022005, 2221102, JPMJSP213)
- Japan Science and Technology Agency (JST) SPRING (18K06660, 20K07052, 21H02650, 18K16081, 2021103, 2022005, 2221102, JPMJSP213)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- statins, p53, TAZ, Hippo signaling pathway, simvastatin, fluvastatin, p53 transcriptional activation, tumor cell survival, combination cancer therapy, tumor suppressor
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