Mechanistic study of ELF3 regulating growth and metastasis of epithelial ovarian cancer through the PI3K/AKT signaling pathway
FU Xin
ZHANG Lei
TAO Ziqi
MAO Yepeng
LIU Shuna
WANG Ting
LI Rong
XU Juan
LOU Jianfang
WANG Fang
Abstract：Objective To investigate the expression of E74-like ETS transcription factor 3(ELF3)in epithelial ovarian cancer(EOC)tissues and its relationship with clinicopathological features,and to preliminarily analyze the role and molecular mechanism of ELF3 in promoting EOC cell growth and metastasis.Methods Immunohistochemistry was used to detect the expression level of ELF3 in EOC tissues and analyze its correlation with clinicopathological characteristics.ELF3-knockdown A2780 and CAOV3 cell lines,as well as ELF3-overexpressing SKOV3 cell lines,were constructed.The effects of ELF3 on cell proliferation and metastatic ability were assessed using the cell counting kit-8(CCK-8)assay,scratch wound healing assay,and Transwell migration and invasion assays.Subcutaneous xenograft and intraperitoneal metastasis models were established in nude mice to evaluate the role of ELF3 in tumor growth and metastasis in vivo.Western blotting was performed to examine the effects of ELF3 on the expression of epithelial-mesenchymal transition(EMT)markers,namely neural cadherin(N-cadherin)and epithelial cadherin(E-cadherin),and on the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)signaling pathway.A PI3K inhibitor LY294002 was used to validate the regulatory role of this pathway in EMT.Results Immunohistochemical results showed that high expression of ELF3 was significantly associated with International Federation of Gynecology and Obstetrics(FIGO)stage,lymph node metastasis,peritoneal metastasis and the presence of ascites(P＜0.05).Serum levels of cancer antigen 125,cancer antigen 153,and human epididymis protein 4 were significantly elevated in the high ELF3 expression group(P＜0.05).In vitro experiments demonstrated that ELF3 knockdown significantly inhibited EOC cell proliferation,migration,and invasion(P＜0.001),whereas ELF3 overexpression promoted these processes(P＜0.05).In animal models,the tumor volume and the number of Ki-67 positive cells in the ELF3 knockdown group were significantly lower than those in the control group(58.50±7.06 vs.87.83±3.87,P＜0.05),and the number of intraperitoneal metastatic nodules was also significantly reduced(3.50±0.50 vs.8.50±1.12,P＜0.01).Compared with the control group,N-cadherin protein levels were significantly downregulated,and E-cadherin expression was upregulated in ELF3-knockdown A2780 cells and xenograft tumors from the knockdown group.In ELF3-overexpressing SKOV3 cells,the expression levels of phosphorylated PI3K(p-PI3K)and phosphorylated AKT(p-AKT)were increased,while total PI3K and AKT expression showed no significant change.Following treatment with a PI3K inhibitor(LY294002),p-AKT and N-cadherin expression were significantly downregulated,and E-cadherin expression was upregulated,whereas ELF3 expression remained unchanged.Conclusion ELF3 is highly expressed in EOC tissues and promotes tumor growth and metastasis,potentially regulating EMT-related proteins through the PI3K/AKT pathway to participate in the progression of EOC.
Keywords：epithelial ovarian cancerE74-like ETS transcription factor 3growthmetastasisinvasion
Publication Date：2026-02-28
Online Publishing Date：2026-04-01(First online date of this platform, not the publication date of the document)
Pages：8( 113-120 )