title: Targeting SALL4 by entinostat in lung cancer.
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.
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore.
authors.forename: Kol Jia
authors.initials: KJ
authors.lastname: Yong
authors.affiliation: Department of Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Ailing
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.|Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou, China.
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Ou
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore.
authors.forename: Clarice Kit Yee
authors.initials: CK
authors.lastname: Hong
authors.affiliation: Department of Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Wenxiu
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Hiro
authors.initials: H
authors.lastname: Tatetsu
authors.affiliation: Department of Laboratory Medicine, National University Hospital, National University Health System, Singapore.
authors.forename: Benedict
authors.initials: B
authors.lastname: Yan
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore.
authors.forename: Lihua
authors.initials: L
authors.lastname: Qi
authors.affiliation: Department of Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Fletcher
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore.
authors.forename: Henry
authors.initials: H
authors.lastname: Yang
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore.
authors.forename: Ross
authors.initials: R
authors.lastname: Soo
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore.|Harvard Stem Cell Institute, Boston, MA, USA.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Tenen
authors.affiliation: Department of Pathology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Chai
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D004195:Disease Models, Animal; D015870:Gene Expression; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms; D051379:Mice; D011725:Pyridines / Q000494:pharmacology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D014157:Transcription Factors / Q000037:antagonists & inhibitors*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D056572:Histone Deacetylase Inhibitors; D011725:Pyridines; D034741:RNA, Small Interfering; C472575:SALL4 protein, human; D014157:Transcription Factors; C118739:entinostat
keywords: HDAC inhibitor; SALL4; entinostat; lung cancer