Oncotarget

Research Papers:

ELF3 is a negative regulator of epithelial-mesenchymal transition in ovarian cancer cells

Tsz-Lun Yeung, Cecilia S. Leung, Kwong-Kwok Wong, Arthur Gutierrez-Hartmann, Joseph Kwong, David M. Gershenson and Samuel C. Mok _

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Oncotarget. 2017; 8:16951-16963. https://doi.org/10.18632/oncotarget.15208

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Abstract

Tsz-Lun Yeung1, Cecilia S. Leung1, Kwong-Kwok Wong1, Arthur Gutierrez-Hartmann2, Joseph Kwong3, David M. Gershenson1, Samuel C. Mok1

1Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

2Anschutz Medical Campus, University of Colorado Denver, Aurora, CO, USA

3Department of Obstetrics and Gynecology, The Chinese University of Hong Kong, Hong Kong

Correspondence to:

Samuel C. Mok, email: scmok@mdanderson.org

Keywords: ovarian carcinoma, ELF3, epithelial-mesenchymal transition, mesenchymal-epithelial transition, patient survival

Received: December 16, 2016     Accepted: January 27, 2017     Published: February 09, 2017

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.


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