title: ELF3 is a negative regulator of epithelial-mesenchymal transition in ovarian cancer cells.
abstract: Transcription factors are master switches for various biochemical pathways. However, transcription factors involved in the pathogenesis of ovarian cancer have yet to be explored thoroughly. Therefore, in the present study, we assessed the prognostic value of the transcription factor E74-like factor 3 (ELF3) identified via transcriptome profiling of the epithelial components of microdissected ovarian tumor samples isolated from long- and short-term survivors and determined its roles in ovarian cancer pathogenesis. Immunohistochemical analysis of ELF3 in tumor tissue sections suggested that ELF3 was exclusively expressed by epithelial ovarian cancer cells. Furthermore, using 112 high-grade ovarian cancer samples isolated from patients and The Cancer Genome Atlas (TCGA) data, we found that downregulation of ELF3 expression was markedly associated with reduced survival. Functional studies demonstrated that overexpression of ELF3 in ovarian cancer cells suppressed proliferation and anchorage-dependent growth of the cells and that ELF3 silencing increased cell proliferation. Furthermore, upregulation of ELF3 increased expression of epithelial markers, decreased expression of mesenchymal markers, and mediated translocation of epithelial-mesenchymal transition (EMT) signaling molecules in ovarian cancer cells. Finally, we validated the tumor-inhibitory roles of ELF3 using animal models. In conclusion, ELF3 is a favorable prognostic marker for ovarian cancer. As a negative regulator of EMT, ELF3-modulated reversal of EMT may be a new effective modality in the treatment of ovarian cancer.
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Tsz-Lun
authors.initials: TL
authors.lastname: Yeung
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Cecilia S
authors.initials: CS
authors.lastname: Leung
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Kwong-Kwok
authors.initials: KK
authors.lastname: Wong
authors.affiliation: Anschutz Medical Campus, University of Colorado Denver, Aurora, CO, USA.
authors.forename: Arthur
authors.initials: A
authors.lastname: Gutierrez-Hartmann
authors.affiliation: Department of Obstetrics and Gynecology, The Chinese University of Hong Kong, Hong Kong.
authors.forename: Joseph
authors.initials: J
authors.lastname: Kwong
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Gershenson
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Samuel C
authors.initials: SC
authors.lastname: Mok
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods* / Q000706:statistics & numerical data; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D018613:Microscopy, Confocal; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017741:Survivors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C105529:ELF3 protein, human; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors
keywords: ELF3; epithelial-mesenchymal transition; mesenchymal-epithelial transition; ovarian carcinoma; patient survival