TY - JOUR
T1 - ELF3 is a negative regulator of epithelial-mesenchymal transition in ovarian cancer cells
AU - Yeung, Tsz Lun
AU - Leung, Cecilia S.
AU - Wong, Kwong Kwok
AU - Gutierrez-Hartmann, Arthur
AU - Kwong, Joseph
AU - Gershenson, David M.
AU - Mok, Samuel C.
N1 - Funding Information:
This study was supported in part by grants R01CA133057 (to S.C.M.), R01CA169200 (to S.C.M.) and the MD Anderson Ovarian Cancer Specialized Program of Research Excellence grant (P50CA083639; to S.C.M.) from the National Institutes of Health. This research was also supported in part by grant POE/MDCAA/02.201101 (to T.-L.Y.) from the Ovarian Cancer Research Fund and the Louisa M. McGregor Ovarian Cancer Foundation, and the National Institutes of Health/National Cancer Institute under award number P30CA016672.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - ELF3
KW - Epithelial-mesenchymal transition
KW - Mesenchymal-epithelial transition
KW - Ovarian carcinoma
KW - Patient survival
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U2 - 10.18632/oncotarget.15208
DO - 10.18632/oncotarget.15208
M3 - Article
C2 - 28199976
AN - SCOPUS:85014702473
SN - 1949-2553
VL - 8
SP - 16951
EP - 16963
JO - Oncotarget
JF - Oncotarget
IS - 10
ER -