FUT8 drives the proliferation and invasion of trophoblastic cells via IGF-1/IGF-1R signaling pathway.
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.
['Yu|Ming|M|', 'Cui|Xinyuan|X|', 'Wang|Hao|H|', 'Liu|Jianwei|J|', 'Qin|Huamin|H|', 'Liu|Shuai|S|', 'Yan|Qiu|Q|']
D002460:Cell Line D049109:Cell Proliferation D005647:Fucosyltransferases D006801:Humans D007334:Insulin-Like Growth Factor I D017526:Receptor, IGF Type 1 D015398:Signal Transduction D014327:Trophoblasts
FUT8 Trophoblasts IGF-1R Implantation