点击次数：

论文类型：期刊论文

发表时间：2019-11-01

发表刊物：JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY

收录刊物：PubMed、SCIE

卷号：75

期号：4

页面范围：549-559

ISSN号：1138-7548

关键字：Caveolin-1; Rfng; MAPK; Hnf4a; Sp1; HCC

摘要：Caveolin-1 (Cav-1) is a critical structural protein of caveolae and plays an oncogene-like role by participating in abnormal protein glycosylation in hepatocellular carcinoma (HCC). However, the mechanism by which Cav-1 regulates glycosylation and glycosyltransferase expression has not been completely defined. Here, we show that Cav-1 promotes the expression of Rfng, which is a beta-1,3-N-acetylglucosaminyltransferase included in the Fringe family. In this study, we showed that the mouse HCC cell line, Hepa1-6, with low Rfng transcription and protein levels, lacked Cav-1 expression, whereas strong Rfng expression was found in the mouse HCC cell line Hca-F, with high transcription and protein levels for Cav-1. Subsequently Cav-1 overexpression in Hepa1-6 was found to activate mitogen-activated protein kinase (MAPK) signaling and induce phosphorylation of the transcription factors Hnf4a and Sp1, which bind to the Rfng promoter region to promote its transcription. On the contrary, when knocking down Cav-1 expression in Hca-F, the activity of the MAPK pathway was significantly inhibited, and phosphorylation of Hnf4a, Sp1 and the expression of Rfng were attenuated. These data reveal that Cav-1 promotes phosphorylation of transcription factors Hnf4a and Sp1, which bind to the Rfng promoter region, via the MAPK signaling pathway, to induce the transcription of Rfng. Our current findings provide molecular genetic evidence that Cav-1 plays an important role in regulating glycosyltransferase expression and may participate in the abnormal glycosylation that mediates the invasion and metastasis of HCC.