FUT8 drives the proliferation and invasion of trophoblastic cells via IGF-1/IGF-1R signaling pathway. (January 2019)

• Record Type: Journal Article
• Authors: Yu, Ming; Cui, Xinyuan; Wang, Hao; Liu, Jianwei; Qin, Huamin; Liu, Shuai; Yan, Qiu
• Is Part Of: Placenta. Volume 75(2019)
• Page Start: 45
• Page End: 53
• Publication Date: 2019-01
• Subjects: Implantation -- Trophoblasts -- FUT8 -- IGF-1R; DAPI 2-(4-amidinophenyl)-6-indolecarbamidine -- EVTs extravillous trophoblasts -- EMT epithelial-mesenchymal transition -- FUT8 α1, 6-fucosyltransferase VIII -- IGF-1 Insulin-like growth factor 1 -- IGF-1R Insulin-like growth factor 1 receptor -- LCA Lens culinaris -- MAPK Mitogen-activated protein kinase -- MMP-2 Matrix metalloprotein 2 -- MMP-9 Matrix metalloprotein 9 -- PCNA Proliferating cell nuclear antigen -- PI3K Phosphoinositide 3-kinase; Placenta -- Periodicals; Reproduction -- Periodicals; Placenta -- Periodicals; Placenta -- Périodiques; Reproduction -- Périodiques; 612.63
• DOI: 10.1016/j.placenta.2018.11.005
• Languages: English
• ISSNs: 0143-4004

Abstract

Abstract: Introduction: Trophoblast proliferation and invasion are essential for embryo implantation and placentation. Protein glycosylation is one of the most common and vital post-translational modifications, regulates protein physical and biochemical properties. FUT8 is the only known fucosyltransferase responsible for catalyzing α1, 6-fucosylation in mammals, and α1, 6-fucosylated glycoproteins are found to participate in various physiopathological processes. However, whether FUT8/α1, 6-fucosylation modulates the functions of trophoblastic cells remains elusive. Methods: FUT8 in human placenta villi during 6-8 gestational weeks and trophoblastic cells were detected by Western blot and immunofluorescent staining. α1, 6-fucosylation in tissues or cells were measured by Lectin LCA ( Lens culinaris ) fluorescent staining and Lectin blot. FUT8 expression was down-regulated by siRNA transfection in JAR and JEG-3 cells, and cell viability, motility and invasiveness ability were detected by the functional experiments. α1, 6-fucosylation of insulin-like growth factor receptor (IGF-1R) was examined by immunoprecipitation, and the amount of phosphorylated IGF-1R was detected in FUT8 down-regulated JAR cells. Results: Human placenta villi and trophoblastic cells expressed FUT8/α1, 6-fucosylation. Knockdown FUT8 by siRNA transfection suppressed the proliferation, epithelial-mesenchymal transition, migration and invasion of JAR and JEG-3 cells. Furthermore, we found that FUT8 modified the α1, 6-fucosylation of IGF-1R, and regulated IGF-1 dependent activation of IGF-1R, MAPK and PI3K/Akt signaling pathways in JAR cells. Conclusions: Our results implicate a critical role for FUT8 in maintaining the normal functions of trophoblastic cells, suggesting manipulating FUT8 may be an effective approach in pregnancy. Highlights: Human placenta villi from the first trimester express FUT8 and α1, 6-fucosylation. FUT8 facilitates the proliferation, migration and invasion of trophoblastic cells. FUT8 modifies the α1, 6-fucosylatioin of IGF-1R, and regulates the IGF-1R activation.