PMID- 27787520
OWN - NLM
STAT- MEDLINE
DCOM- 20170828
LR  - 20181113
IS  - 2041-4889 (Electronic)
VI  - 7
IP  - 10
DP  - 2016 Oct 27
TI  - Increased expression of EHF via gene amplification contributes to the activation 
      of HER family signaling and associates with poor survival in gastric cancer.
PG  - e2442
LID - 10.1038/cddis.2016.346 [doi]
AB  - The biological function of E26 transformation-specific (ETS) transcription factor 
      EHF/ESE-3 in human cancers remains largely unknown, particularly gastric cancer. 
      The aim of this study was to explore the role of EHF in tumorigenesis and its 
      potential as a therapeutic target in gastric cancer. By using quantitative RT-PCR 
      (qRT-PCR), immunohistochemistry (IHC) and fluorescence in situ hybridization 
      (FISH) assays, we investigated the expression and copy number of EHF in a cohort 
      of gastric cancers and control subjects. Specific EHF siRNAs was used to 
      determine the biologic impacts and mechanisms of altered EHF expression in vitro 
      and in vivo. Dual-luciferase reporter, chromatin immunoprecipitation (ChIP) and 
      electrophoretic mobility shift assay (EMSA) assays were performed to identify its 
      downstream targets. Our results demonstrated that EHF was significantly 
      upregulated and frequently amplified in gastric cancer tissues as compared with 
      control subjects. Moreover, EHF amplification was positively correlated with its 
      overexpression and significantly associated with poor clinical outcomes of 
      gastric cancer patients. We also found that EHF knockdown notably inhibited 
      gastric cancer cell proliferation, colony formation, migration, invasion and 
      tumorigenic potential in nude mice and induced cell cycle arrest and apoptosis. 
      Importantly, we identified EHF as a new HER2 transcription factor and the 
      modulator of HER3 and HER4 in gastric cancer. Collectively, our findings suggest 
      that EHF is a novel functional oncogene in gastric cancer by regulating the human 
      epidermal growth factor receptor (HER) family of receptor tyrosine kinases and 
      may represent a potential prognostic marker and therapeutic target for this 
      cancer.
FAU - Shi, Jing
AU  - Shi J
AD  - Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an 710061, China.
FAU - Qu, Yiping
AU  - Qu Y
AD  - Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an 710061, China.
FAU - Li, Xinru
AU  - Li X
AD  - Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an 710061, China.
FAU - Sui, Fang
AU  - Sui F
AD  - Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an 710061, China.
FAU - Yao, Demao
AU  - Yao D
AD  - Department of Surgery, The First Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an 710061, China.
FAU - Yang, Qi
AU  - Yang Q
AD  - Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an 710061, China.
FAU - Shi, Bingyin
AU  - Shi B
AD  - Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an 710061, China.
AD  - Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First 
      Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
FAU - Ji, Meiju
AU  - Ji M
AD  - Center for Translational Medicine, The First Affiliated Hospital of Xi'an 
      Jiaotong University, Xi'an 710061, China.
FAU - Hou, Peng
AU  - Hou P
AD  - Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an 710061, China.
AD  - Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First 
      Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20161027
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (EHF protein, human)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
SB  - IM
MH  - Animals
MH  - Apoptosis/genetics
MH  - Cell Cycle Checkpoints/genetics
MH  - Cell Line, Tumor
MH  - Cell Movement/genetics
MH  - Cell Proliferation
MH  - Epithelial-Mesenchymal Transition/genetics
MH  - *Gene Amplification
MH  - Gene Expression Regulation, Neoplastic
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Male
MH  - Mice, Nude
MH  - Neoplasm Invasiveness
MH  - Protein-Tyrosine Kinases/*metabolism
MH  - Signal Transduction/*genetics
MH  - Stomach Neoplasms/*genetics/*pathology
MH  - Survival Analysis
MH  - Transcription Factors/*genetics/metabolism
MH  - Treatment Outcome
MH  - Xenograft Model Antitumor Assays
PMC - PMC5134001
EDAT- 2016/10/28 06:00
MHDA- 2017/08/29 06:00
PMCR- 2016/10/01
CRDT- 2016/10/28 06:00
PHST- 2016/03/31 00:00 [received]
PHST- 2016/09/04 00:00 [revised]
PHST- 2016/09/26 00:00 [accepted]
PHST- 2016/10/28 06:00 [pubmed]
PHST- 2017/08/29 06:00 [medline]
PHST- 2016/10/28 06:00 [entrez]
PHST- 2016/10/01 00:00 [pmc-release]
AID - cddis2016346 [pii]
AID - 10.1038/cddis.2016.346 [doi]
PST - epublish
SO  - Cell Death Dis. 2016 Oct 27;7(10):e2442. doi: 10.1038/cddis.2016.346.