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Cited by 41Histone Deacetylase Inhibitors ResearchLung Cancer Research StudiesEpigenetics and DNA Methylation

Targeting SALL4 by entinostat in lung cancer

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Yong, Kol Jia, Li, Ailing, Ou, Wen-Bin, Hong, Clarice Kit Yee, Zhao, Wenxiu, Wang, Fei, Tatetsu, Hiro, Yan, Benedict +6 more·2016·Oncotarget
DOI 10.18632/oncotarget.12251PMC PMC5342750
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Abstract

// Kol Jia Yong 1, * , Ailing Li 2, * , Wen-Bin Ou 2, 3, * , Clarice Kit Yee Hong 1 , Wenxiu Zhao 2 , Fei Wang 2 , Hiro Tatetsu 2 , Benedict Yan 4 , Lihua Qi 1 , Jonathan A. Fletcher 2 , Henry Yang 1 , Ross Soo 1 , Daniel G. Tenen 1, 5, * , Li Chai 2, * 1 Cancer Science Institute of Singapore, National University of Singapore, Singapore 2 Department of Pathology, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA, USA 3 Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, China 4 Department of Laboratory Medicine, National University Hospital, National University Health System, Singapore 5 Harvard Stem Cell Institute, Boston, MA, USA * These authors have contributed equally to this work Correspondence to: Li Chai, email: lchai@partners.org Keywords: entinostat, HDAC inhibitor, lung cancer, SALL4 Received: March 08, 2016 Accepted: September 13, 2016 Published: September 26, 2016 ABSTRACT The overall survival of lung cancer patients remains dismal despite the availability of targeted therapies. Oncofetal protein SALL4 is a novel cancer target. We herein report that SALL4 was aberrantly expressed in a subset of lung cancer patients with poor survival. SALL4 silencing by RNA interference or SALL4 peptide inhibitor treatment led to impaired lung cancer cell growth. Expression profiling of SALL4-knockdown cells demonstrated that both the EGFR and IGF1R signaling pathways were affected. Connectivity Map analysis revealed the HDAC inhibitor entinostat as a potential drug in treating SALL4-expressing cancers, and this was confirmed in 17 lung cancer cell lines. In summary, we report for the first time that entinostat can target SALL4-positive lung cancer. This lays the foundation for future clinical studies evaluating the therapeutic efficacy of entinostat in SALL4-positive lung cancer patients.

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Authors
Yong, K. J., Li, A., Ou, W.-B., Hong, C. K. Y., Zhao, W., Wang, F., Tatetsu, H., Yan, B., Qi, L., Fletcher, J. A., Yang, H., Soo, R., Tenen, D. G., & Chai, L.
Affiliations
  • National University of Singapore (SG)
  • Brigham and Women's Hospital (US)
  • Cancer Science Institute of Singapore, National University of Singapore, Singapore
  • National University Hospital (SG)
  • Harvard University (US)
Corresponding author
  • Yong, Kol Jia
  • Li, Ailing
  • Ou, Wen-Bin
  • Tenen, Daniel G.
  • Chai, Li
ORCID
Venue
Oncotarget
Publisher
Impact Journals, LLC
Published
2016-09-26
Volume
7
Issue
46
Pages
75425-75440
ISSN
1949-2553 (ISSN-L)
DOI
10.18632/oncotarget.12251
PMC
PMC5342750
OpenAlex
W2526123284
Cited by
41
References
50
Citations by year
2026: 5 · 2025: 3 · 2024: 1 · 2023: 10 · 2022: 4 · 2021: 4 · 2020: 5 · 2019: 6 · 2018: 2 · 2017: 1
FWCI
1.56
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Oncotarget (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
  • National University of Singapore (submittedVersion)
Funders
  • National Research Foundation
  • National Research Foundation Singapore
  • Zhejiang Sci-Tech University (14042107-Y)
  • National Institutes of Health
  • Medical Research Council
  • National Medical Research Council
  • National Heart, Lung, and Blood Institute (P01HL095489, P01HL131477)
  • National Cancer Institute (P50CA127003, R35CA197697)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
  • Health Sciences › Medicine › Oncology › Lung Cancer Research Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
SALL4, entinostat, lung cancer, histone deacetylase inhibitors, oncofetal protein, EGFR signaling, IGF1R signaling, drug repurposing, Connectivity Map
MeSH terms
Animals, Antineoplastic Agents, Benzamides, Cell Survival, Disease Models, Animal, Humans, Lung Neoplasms, Pyridines, Transcription Factors, Gene Expression, Xenograft Model Antitumor Assays, RNA Interference, RNA, Small Interfering, Cell Line, Tumor, Mice, Histone Deacetylase Inhibitors

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