Apolipoprotein E enhances migration of endometrial cancer cells byactivating the ERK/MMP9 signaling pathway.
10.12122/j.issn.1673-4254.2023.02.11
- Author:
Chao Ying WU
1
;
Wen Jun CHENG
2
Author Information
1. Department of Gynecology, Changzhou Maternity and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, China.
2. Department of Gynecology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
- Publication Type:Journal Article
- Keywords:
apolipoprotein E;
cell migration;
endometrial carcinoma;
extracellular signal-regulated kinases
- MeSH:
Female;
Humans;
Matrix Metalloproteinase 9/metabolism*;
Cell Line, Tumor;
Signal Transduction;
Endometrial Neoplasms/genetics*;
Cell Proliferation;
Apoptosis;
Cell Movement;
RNA, Small Interfering;
Apolipoproteins E;
Apolipoproteins/pharmacology*
- From:
Journal of Southern Medical University
2023;43(2):232-241
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To study the role of apolipoprotein E (APOE) in regulating endometrial cancer metastasis and explore the signaling pathway in the regulatory mechanism.
METHODS:Human endometrial cancer cell line HEC-1B was transfected with a control siRNA (siCtrl) or a specific siRNA targeting APOE (siAPOE) or with either pEGFP-N1 plasmid or an APOEoverexpressing plasmid. The changes in migration, proliferation, apoptosis and cell cycle of the transfected cells were examined using wound healing assay, Transwell migration assay, MTT assay, flow cytometry, and Hoechst staining. The activity of the ERK/MMP9 signaling pathway in the transfected cells was assessed using RT-qPCR and Western blotting. The expression level of APOE in clinical specimens of endometrial cancer tissues were detected using immunohistochemistry and its correlation with differentiation of endometrial cancer tissues was analyzed.
RESULTS:Wound healing assay and Transwell migration assay showed that compared with those in siCtrl group, HEC-1B cells transfected with siAPOE showed significantly reduced migration ability (P < 0.05), whereas APOE overexpression significantly promoted the migration of the cells (P < 0.05). Neither APOE knockdown nor overexpression produced significant effects on HEC-1B cell proliferation as shown by MTT assay and flow cytometry. Hoechst staining revealed that transfection with siAPOE did not significantly affect apoptosis of HEC-1B cells. APOE knockdown obviously reduced and APOE overexpression enhanced ERK phosphorylation and MMP9 expression in HEC-1B cells (P < 0.05). Treatment with U0126 partially reversed the effects of APOE overexpression on ERK phosphorylation, migration and MMP9 expression in HEC-1B cells (P < 0.05). APOE is highly expressed in clinical samples of endometrial cancer tissues as compared with the adjacent tissues.
CONCLUSION:APOE is highly expressed in endometrial cancer tissues to promote cancer cell migration by enhancing ERK phosphorylation and MMP9 expression.
