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Cited by 49Histone Deacetylase Inhibitors ResearchMechanisms of cancer metastasisHead and Neck Cancer Studies

HDAC4 promotes nasopharyngeal carcinoma progression and serves as a therapeutic target

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Cheng, Chun, Yang, Jun, Li, Si-Wei, Huang, Guofu, Li, Chenxi, Min, Wei-Ping, Sang, Yi·2021·Cell Death & Disease
DOI 10.1038/s41419-021-03417-0PMC PMC7862285
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Abstract

Histone deacetylases (HDACs) are involved in tumor progression, and some have been successfully targeted for cancer therapy. The expression of histone deacetylase 4 (HDAC4), a class IIa HDAC, was upregulated in our previous microarray screen. However, the role of HDAC4 dysregulation and mechanisms underlying tumor growth and metastasis in nasopharyngeal carcinoma (NPC) remain elusive. Here, we first confirmed that the HDAC4 levels in primary and metastatic NPC tissues were significantly increased compared with those in normal nasopharyngeal epithelial tissues and found that high HDAC4 expression predicted a poor overall survival (OS) and progression-free survival (PFS). Functionally, HDAC4 accelerated cell cycle G1/S transition and induced the epithelial-to-mesenchymal transition to promote NPC cell proliferation, migration, and invasion in vitro, as well as tumor growth and lung metastasis in vivo. Intriguingly, knockdown of N-CoR abolished the effects of HDAC4 on the invasion and migration abilities of NPC cells. Mechanistically, HDAC3/4 binds to the E-cadherin promoter to repress E-cadherin transcription. We also showed that the HDAC4 inhibitor tasquinimod suppresses tumor growth in NPC. Thus, HDAC4 may be a potential diagnostic marker and therapeutic target in patients with NPC.

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  • Tasquinimod, a specific inhibitor of HDAC4, effectively inhibits growth and metastasis of tumor cells in vitro and in vivo.

    “tasquinimod, a specific inhibitor of HDAC4, has been shown to effectively inhibit the growth and metastasis of tumor cells both in vitro and in vivo15.”

    From An HDAC4-specific PROTAC degrader achieves radiation sensitization by enhancing ferroptosis in lung cancer (2026) · cites this paper as [15]

    The Results report that tasquinimod reduced NPC-cell proliferation, migration, and invasion in vitro and tumor growth in vivo (Figs. 5–7). They do not report an in vivo metastasis result. The paper also describes tasquinimod as HDAC4-selective but notes a predicted interaction with HDAC7, so calling it a specific HDAC4 inhibitor is stronger than the evidence shown. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • HDAC4 is a member of class IIa HDACs, which play a role in tumorigenesis of multiple cancers.

    “Histone deacetylase 4 (HDAC4) is a member of the class IIa HDACs, which play a role in the tumorigenesis of multiple cancers13–15.”

    From An HDAC4-specific PROTAC degrader achieves radiation sensitization by enhancing ferroptosis in lung cancer (2026) · cites this paper as [15]

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Research works printed but not linked: 31

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Cited by

Sorted by citations

Authors
Cheng, C., Yang, J., Li, S.-W., Huang, G., Li, C., Min, W.-P., & Sang, Y.
Affiliations
  • Third Affiliated Hospital of Nanchang University (CN)
  • Western University (CA)
Corresponding author
Sang, Yi
ORCID
Venue
Cell Death & Disease
Publisher
Springer Science and Business Media LLC
Published
2021-02-01
Volume
12
Issue
2
Pages
137-137
ISSN
2041-4889 (ISSN-L)
DOI
10.1038/s41419-021-03417-0
PMC
PMC7862285
OpenAlex
W3126781502
Cited by
49
References
3
Citations by year
2026: 3 · 2025: 4 · 2024: 9 · 2023: 18 · 2022: 13 · 2021: 2
FWCI
3.29
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Death and Disease (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
the National Science Foundation of China
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
  • Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
Keywords
HDAC4, nasopharyngeal carcinoma, histone deacetylase, class IIa HDACs, NCoR, E-cadherin, epithelial-mesenchymal transition, G1/S transition, tumor cell migration and invasion, lung metastasis, tasquinimod, prognostic factors, therapeutic target
MeSH terms
Nasopharyngeal Carcinoma, Animals, Histone Deacetylases, Humans, Mice, Nude, Repressor Proteins, Disease Progression, Mice

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