MGAT1 is a novel transcriptional target of Wnt/β-catenin signaling pathway

Abstract

BackgroundThe Wnt/β-catenin signaling pathway is an evolutionary conserved pathway, which has important functions in vertebrate early development, axis formation, cellular proliferation and morphogenesis. Additionally, Wnt/β-catenin signaling pathway is one of the most important intracellular pathways that controls cancer progression. To date most of the identified targets of this pathway are shown to harbor tumorigenic properties. We previously showed that Mannosyl glycoprotein acetylglucosaminyl-transferase (MGAT1) enzyme is among the Wnt/β-catenin signaling putative target genes in hepatocellular carcinoma cell lines (Huh7).MethodsMGAT1 protein levels were determined by Western Blotting from Huh7 cell lines in which Wnt/β-catenin pathway was activated by means of different approaches such as LiCl treatment and mutant β-catenin overexpression. Luciferase reporter assay was used to analyze the promoter activity of MGAT1. The mRNA levels of MGAT1 were determined by quantitative real-time PCR from Huh7 cells that were treated with either Wnt agonist or GSK-3β inhibitor. Wound healing and XTT cell proliferation assays were performed in order to determine the proliferation and migration capacities of MGAT1 overexpressing stable Huh7 cells. Finally, xenograft experiments were carried out to measure the tumor formation capacities in vivo.ResultsIn this study we showed that the activation of Wnt/β-catenin pathway culminates in the upregulation of MGAT1 enzyme both at transcriptional and post-transcriptional levels. We also showed that overexpression of the β-catenin gene (CTNNB1) increased the promoter activity of MGAT1. We applied a set of complementary approaches to elucidate the functional importance of MGAT1 as a vital target of Wnt/β-catenin signaling in Huh7 cells. Our analyses related to cell proliferation and migration assays showed that in comparison to the control cells, MGAT1 expressing Huh7 cells have greater proliferative and invasive capabilities. Furthermore, the stable overexpression of MGAT1 gene in Huh7 cell lines lead to a significant increase in tumor growth rate in Severe Combined Immunodeficient (SCID) mice.ConclusionsTaken together, we showed for the first time that MGAT is a novel Wnt/β-catenin pathway target that has important implications for tumorigenesis.

Induced pluripotent stem cell‐derived conditional medium promotes Leydig cell anti‐apoptosis and proliferation via autophagy and Wnt/β‐catenin pathway

“…At the same time, all proteins could be up‐regulated by exogenous bFGF added into DMEM‐LG. Furthermore, those proteins could also be up‐regulated by LiCl (20 mmol/L) added into DMEM‐LG, which is a widely used in the activation of Wnt/β‐catenin signalling . However, those proteins were again down‐regulated in iPS‐CM by XAV939 (XAV, 10 μmol/L) (Figure D,E), an inhibitor of the Wnt/β‐catenin signalling pathway .…”

“…22 The results of Western blotting analysis showed that the levels of b-catenin and its target proteins cyclin D1, c-Myc and survivin in iPS-CM group were higher than those in Furthermore, those proteins could also be up-regulated by LiCl (20 mmol/L) added into DMEM-LG, which is a widely used in the activation of Wnt/b-catenin signalling. 39,40 However, those proteins were again down-regulated in iPS-CM by XAV939 (XAV, 10 lmol/L) ( Figure 6D,E), an inhibitor of the Wnt/b-catenin signalling pathway. 41 These results indicated that iPS-CM might be mainly relied on inherent bFGF to promote the proliferation of ILCs through Wnt/ b-catenin signalling pathway.…”

TSN inhibits cell proliferation, migration, invasion, and EMT through regulating miR-874/HMGB2/β-catenin pathway in gastric cancer

“…β-catenin is defined as an oncogene as well as a critical part in the Wnt pathway [40]. It plays an essential role in regulating cancer cell progression, early vertebrate development, and axis formation [41]. HMGB2 was found to be involved in the activation of the Wnt/β-catenin signaling pathway during GC development.…”

Identification of Prognostic Genes in Leiomyosarcoma by Gene Co-Expression Network Analysis

“…Stable overexpression of the MGAT1 gene in the Huh7 cell line resulted in a significant increase in tumor growth rate in severe combined immunodeficiency (SCID) mice. Down-regulation of MGAT1 expression in the liver can significantly reduce hepatic steatosis in mice, while reducing body weight and increasing glucose tolerance (Lee et al, 2012;Akiva and Birgul Iyison, 2018).…”