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Targeting SALL4 by Entinostat in Lung Cancer (Oncotarget, Sep 2016)

Yong KJ1, Li A2, Ou WB2,3, Hong CK1, Zhao W2, Wang F2, Tatetsu H2, Yan B4, Qi L1, Fletcher JA2, Yang H1, Soo R1, Tenen DG1,5, Chai L2

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.

Abstract:

The overall survival of lung cancer patients remains dismal despite the availability of targeted therapies. Oncofetal protein SALL4 is a novelcancer 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 inhibitorentinostat 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.

KEYWORDS: HDAC inhibitor; SALL4; entinostat; lung cancer

PMID: 27705911