HDAC11 is a novel drug target in carcinomas
Abstract
Inhibition of histone deacetylase (HDAC) activity as stand-alone or combination therapy represents a promising therapeutic approach in oncology. The pan- or class I HDAC inhibitors (HDACi) currently approved or in clinical studies for oncology give rise to dose-limiting toxicities, presumably because of the inhibition of several HDACs. This could potentially be overcome by selective blockade of single HDAC family members. Here we report that HDAC11, the most recently identified zinc-dependent HDAC, is overexpressed in several carcinomas as compared to corresponding healthy tissues. HDAC11 depletion is sufficient to cause cell death and to inhibit metabolic activity in HCT-116 colon, PC-3 prostate, MCF-7 breast and SK-OV-3 ovarian cancer cell lines. The antitumoral effect induced can be mimicked by enforced expression of a catalytically impaired HDAC11 variant, suggesting that inhibition of the enzymatic activity of HDAC11 by small molecules could trigger the desired phenotypic changes. HDAC11 depletion in normal cells causes no changes in metabolic activity and viability, strongly suggesting that tumor-selective effects can be achieved. Altogether, our data show that HDAC11 plays a critical role in cancer cell survival and may represent a novel drug target in oncology.
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HDAC11 expression is upregulated in multiple carcinomas compared to healthy counterparts.
“As reported for other HDACs, HDAC11 expression is upregulated in multiple carcinomas compared to healthy counterparts (Deubzer et al., 2012;Gong, Zeng, Yi, & Wu, 2019;Liu, Wu, Jin, Chang, & Xu, 2020).”
From HDACs and the epigenetic plasticity of cancer cells: target the complexity (2022) · cites this paper as Deubzer et al., 2012
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- Authors
- Deubzer, H. E., Schier, M. C., Oehme, I., Lodrini, M., Haendler, B., Sommer, A., & Witt, O.
- Affiliations
- German Cancer Research Center (DE)
- Bayer (Germany) (DE)
- Corresponding author
- Deubzer, Hedwig E.
- Venue
- International Journal of Cancer
- Publisher
- Wiley
- Published
- 2012-10-25
- Volume
- 132
- Issue
- 9
- Pages
- 2200-2208
- ISSN
- 0020-7136 (ISSN-L)
- 1097-0215
- OpenAlex
- W2082426890
- Cited by
- 112
- References
- 29
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 9 · 2023: 9 · 2022: 7 · 2021: 15 · 2020: 10 · 2019: 11 · 2018: 3 · 2017: 9 · 2016: 10 · 2015: 10 · 2014: 7 · 2013: 4
- FWCI
- 2.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Cancer (publishedVersion)
- PubMed (publishedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Enzyme function and inhibition
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- HDAC11, histone deacetylase, carcinoma, tumor cell survival, colon cancer, prostate cancer, breast cancer, ovarian cancer, metabolic activity, therapeutic target
- MeSH terms
- Cells, Cultured, Flow Cytometry, Histone Deacetylases, Humans, Neoplasms, RNA, Messenger, Blotting, Western, Apoptosis, Reverse Transcriptase Polymerase Chain Reaction, Mammary Glands, Human, Cell Proliferation, Caspase 3, Small Molecule Libraries, Histone Deacetylase Inhibitors, Real-Time Polymerase Chain Reaction
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