Molecular mechanisms of syncytin-1 in tumors and placental development related diseases

Abstract

Human endogenous retroviruses (HERVs) have evolved from exogenous retroviruses and account for approximately 8% of the human genome. A growing number of findings suggest that the abnormal expression of HERV genes is associated with schizophrenia, multiple sclerosis, endometriosis, breast cancer, bladder cancer and other diseases. HERV-W env (syncytin-1) is a membrane glycoprotein which plays an important role in placental development. It includes embryo implantation, fusion of syncytiotrophoblasts and of fertilized eggs, and immune response. The abnormal expression of syncytin-1 is related to placental development-related diseases such as preeclampsia, infertility, and intrauterine growth restriction, as well as tumors such as neuroblastoma, endometrial cancer, and endometriosis. This review mainly focused on the molecular interactions of syncytin-1 in placental development-related diseases and tumors, to explore whether syncytin-1 can be an emerging biological marker and potential therapeutic target.

Roles of Human Endogenous Retroviruses and Endogenous Virus-Like Elements in Cancer Development and Innate Immunity

“…Syncytin-1 is an envelope protein of HERV-W. Syncytin-1 is specifically expressed in the human placenta and mediates trophoblast cell fusion in multinucleated syncytiotrophoblast layers [56]. Syncytin-1 is involved in several types of cancers [24,57]. Syncytin-1 is upregulated in endometrial carcinoma, and the overexpression of syncytin-1 can promote cell proliferation, cell cycle progression, and invasion of endometrial carcinoma cells [58,59].…”

The Insertion of an Evolutionary Lost Four-Amino-Acid Cytoplasmic Tail Peptide into a Syncytin-1 Vaccine Increases T- and B-Cell Responses in Mice

“…Syncytin-1 facilitates the fusion of cytotrophoblasts, leading to the formation of the placental syncytiotrophoblast cell layer [ 3 , 4 , 6 ]; furthermore, Syncytin-1 is believed to be involved in maintaining foeto-maternal tolerance [ 7 , 8 ]. The expression of Syncytin-1 is strictly regulated by epigenetic mechanisms [ 9 , 10 ], and the aberrant expression of Syncytin-1 is associated with various pathologies, among others, cancer [ 11 , 12 ]. There is a growing number of reports on the expression of Syncytin-1 and gene products of other HERV-W loci in human cancer cells and tissues at either mRNA or protein levels (reviewed in [ 11 , 13 , 14 , 15 , 16 ]).…”

“…The expression of Syncytin-1 is strictly regulated by epigenetic mechanisms [ 9 , 10 ], and the aberrant expression of Syncytin-1 is associated with various pathologies, among others, cancer [ 11 , 12 ]. There is a growing number of reports on the expression of Syncytin-1 and gene products of other HERV-W loci in human cancer cells and tissues at either mRNA or protein levels (reviewed in [ 11 , 13 , 14 , 15 , 16 ]). The implication of HERV-W/Syncytin-1 expression in cancer is not fully understood, but the expression of HERV-W in cancer makes these antigens potential targets for cancer immunotherapy.…”

Reproductive Immunology and Pregnancy 2.0

“…In addition, the nonfusogenic effects of syncytin may be responsible for pathological placental morphogenesis based on increased apoptosis and proliferation [8]. Disturbed syncytin-1 expression is associated with increased risk of infertility, pre-eclampsia and FGR, but it has also been observed in patients with tumors such as neuroblastomas, endometrial cancer, and endometriosis [8,9]. Poor placental angiogenesis is a typical histopathological feature of syncytin-1 functional disruption and is often found in patients with pre-eclampsia [10].…”