Vorinostat suppresses hypoxia signaling by modulating nuclear translocation of hypoxia inducible factor 1 alpha Article Swipe
Chao Zhang
,
Chunzhang Yang
,
Michael J. Feldman
,
Herui Wang
,
Ying Pang
,
Dominic Maggio
,
Dongwang Zhu
,
Cody L. Nesvick
,
Pauline Dmitriev
,
Petra Bullova
,
Prashant Chittiboina
,
Roscoe O. Brady
,
Karel Pacák
,
Zhengping Zhuang
·
YOU?
·
· 2017
· Open Access
·
· DOI: https://doi.org/10.18632/oncotarget.18125
YOU?
·
· 2017
· Open Access
·
· DOI: https://doi.org/10.18632/oncotarget.18125
Histone deacetylase inhibitors (HDACis) are a potent class of tumor-suppressive agents traditionally believed to exert their effects through loosening tightly-wound chromatin resulting in de-inhibition of various tumor suppressive genes. Recent literature however has shown altered intratumoral hypoxia signaling with HDACi administration not attributable to changes in chromatin structure. We sought to determine the precise mechanism of HDACi-mediated hypoxia signaling attenuation using vorinostat (SAHA), an FDA-approved class I/IIb/IV HDACi. Through an in-vitro and in-vivo approach utilizing cell lines for hepatocellular carcinoma (HCC), osteosarcoma (OS), and glioblastoma (GBM), we demonstrate that SAHA potently inhibits HIF-a nuclear translocation via direct acetylation of its associated chaperone, heat shock protein 90 (Hsp90). In the presence of SAHA we found elevated levels of acetyl-Hsp90, decreased interaction between acetyl-Hsp90 and HIF-a, decreased nuclear/cytoplasmic HIF-α expression, absent HIF-α association with its nuclear karyopharyin Importin, and markedly decreased HIF-a transcriptional activity. These changes were associated with downregulation of downstream hypoxia molecules such as endothelin 1, erythropoietin, glucose transporter 1, and vascular endothelial growth factor. Findings were replicated in an in-vivo Hep3B HRE-Luc expressing xenograft, and were associated with significant decreases in xenograft tumor size. Altogether, this study highlights a novel mechanism of action of an important class of chemotherapeutic.
Related Topics
Concepts
Hypoxia (environmental)
HIF1A
Hypoxia-inducible factors
Hypoxia-Inducible Factor 1
Signal transduction
Vorinostat
Chromosomal translocation
Alpha (finance)
Medicine
Cell biology
Cancer research
Pharmacology
Chemistry
Biology
Transcription factor
Biochemistry
Angiogenesis
Histone deacetylase
Histone
Gene
Oxygen
Nursing
Organic chemistry
Patient satisfaction
Construct validity
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.18632/oncotarget.18125
- http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=download&path%5B%5D=18125&path%5B%5D=58105
- OA Status
- diamond
- Cited By
- 72
- References
- 84
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2617150295
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W2617150295Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.18632/oncotarget.18125Digital Object Identifier
- Title
-
Vorinostat suppresses hypoxia signaling by modulating nuclear translocation of hypoxia inducible factor 1 alphaWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2017Year of publication
- Publication date
-
2017-05-23Full publication date if available
- Authors
-
Chao Zhang, Chunzhang Yang, Michael J. Feldman, Herui Wang, Ying Pang, Dominic Maggio, Dongwang Zhu, Cody L. Nesvick, Pauline Dmitriev, Petra Bullova, Prashant Chittiboina, Roscoe O. Brady, Karel Pacák, Zhengping ZhuangList of authors in order
- Landing page
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https://doi.org/10.18632/oncotarget.18125Publisher landing page
- PDF URL
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https://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=download&path%5B%5D=18125&path%5B%5D=58105Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
diamondOpen access status per OpenAlex
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https://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=download&path%5B%5D=18125&path%5B%5D=58105Direct OA link when available
- Concepts
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Hypoxia (environmental), HIF1A, Hypoxia-inducible factors, Hypoxia-Inducible Factor 1, Signal transduction, Vorinostat, Chromosomal translocation, Alpha (finance), Medicine, Cell biology, Cancer research, Pharmacology, Chemistry, Biology, Transcription factor, Biochemistry, Angiogenesis, Histone deacetylase, Histone, Gene, Oxygen, Nursing, Organic chemistry, Patient satisfaction, Construct validityTop concepts (fields/topics) attached by OpenAlex
- Cited by
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72Total citation count in OpenAlex
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2025: 3, 2024: 7, 2023: 12, 2022: 7, 2021: 13Per-year citation counts (last 5 years)
- References (count)
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84Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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