Oncotarget

Research Papers:

Targeting SALL4 by entinostat in lung cancer

Kol Jia Yong, Ailing Li, Wen-Bin Ou, Clarice Kit Yee Hong, Wenxiu Zhao, Fei Wang, Hiro Tatetsu, Benedict Yan, Lihua Qi, Jonathan A. Fletcher, Henry Yang, Ross Soo, Daniel G. Tenen and Li Chai _

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Oncotarget. 2016; 7:75425-75440. https://doi.org/10.18632/oncotarget.12251

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Abstract

Kol Jia Yong1,*, Ailing Li2,*, Wen-Bin Ou2,3,*, Clarice Kit Yee Hong1, Wenxiu Zhao2, Fei Wang2, Hiro Tatetsu2, Benedict Yan4, Lihua Qi1, Jonathan A. Fletcher2, Henry Yang1, Ross Soo1, Daniel G. Tenen1,5,*, Li Chai2,*

1Cancer Science Institute of Singapore, National University of Singapore, Singapore

2Department of Pathology, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA, USA

3Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, China

4Department of Laboratory Medicine, National University Hospital, National University Health System, Singapore

5Harvard 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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