Upregulation of syncytin-1 promotes invasion and metastasis by activating epithelial-mesenchymal transition-related pathway in endometrial carcinoma

Abstract

Background: Endometrial carcinoma (EC) is the most common and lethal malignancy worldwide. Syncytin-1 is expressed in multiple types of cancer. However, the expression pattern and potential mechanism of syncytin-1 and its clinical significance in EC remain unclear. Materials and methods: We analyzed 130 primary EC specimens from Binzhou Medical University to investigate the clinical role of syncytin-1 in EC by using different advanced pathological stages of EC tissues. Kaplan-Meier analysis was used to measure the overall survival of EC patients. Syncytin-1 expression was analyzed by Western blot assays in HECCL-1 and RL-95-2 cells. Cell proliferation, cycle, migration, and invasion abilities were detected by cell counting kit-8, flow cytometry, and transwell assays. AKT and epithelial-mesenchymal transition (EMT)-related genes were assessed by Western blot assays in HECCL-1 and RL-95-2 cells. Results: Syncytin-1 was upregulated in EC tissues and cells and was related to clinical stages, expression of ER, Ki-67, and overall survival of EC. Functional research revealed that overexpression of syncytin-1 can promote cell proliferation, cell cycle progression, and the migration and invasion of EC cells. Suppression of syncytin-1 expression also inhibited cell proliferation and apoptosis in vitro. The expression of syncytin-1 substantially improved the expression levels of EMT-related genes (vimentin, E-cadherin, slug, and ZEB1) but significantly decreased those of epithelial markers (N-cadherin and snail). In addition, we found that syncytin-1 was not correlated with AKT-related genes (total-AKT, p-AKT, and vinculin). Conclusion: Our results suggested that syncytin-1 may promote aggressive behavior and can serve as a novel prognostic biomarker for EC. Our study provides new insights into the regulatory mechanism of EMT signaling.

Kinesin Family Member C1 (KIFC1) Accelerates Proliferation and Invasion of Endometrial Cancer Cells Through Modulating the PI3K/AKT Signaling Pathway

“…The PI3K/AKT signaling plays a pivotal role in the development of EC by regulating cell proliferation, invasion and EMT. 32 - 34 Hence, we further explored the role of KIFC1 in the regulation of PI3K/AKT signaling cascade. As displayed in Figure 5A , knockdown of KIFC1 reduced the protein expression of p-AKT and p-PI3 K, but had no significant effects on the protein expression of AKT and PI3K in Ishikawa cells.…”

Human Endogenous Retroviruses Are Preferentially Expressed in Mononuclear Cells From Cord Blood Than From Maternal Blood and in the Fetal Part of Placenta

“…For instance, we looked at possible abnormal HERV activation in blood samples from women with recurrent miscarriages, but we did not find any alterations (unpublished data). In contrast, enhanced HERV expression is associated with development and invasion of several cancers, e.g., the up-regulation of syncytin-1 promotes the malignant transformation of hydatidiform moles (32) and the spread of endometrial carcinoma (33), and all malignancies of placental origin (including those of late appearance) derive from cells of the conceptus, not of the mother.…”

Construction and Comprehensive Analysis of the Competing Endogenous Rna Network in Endometrial Adenocarcinoma

“…Although there has been no large population-based case-control study on the correlation between EC and other tumors, Schildkraut et al [33] found a signi cant association between breast cancer and ovarian epithelial tumor with EC in familial cases. In addition, Liu et al [34] found that overexpression of syncytin-1 promoted the invasion and metastasis of EC cells by activating epithelial-to-mesenchymal transitionrelated pathways. Consistently, in this study, the WGCNA con rmed that a history of other malignancies was positively correlated with the MEbrown module.…”