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Caveolin-1 promotes Rfng expression via Erk-Jnk-p38 signaling pathway in mouse hepatocarcinoma cells

  • Cheng Zhang
  • Qiong Wu
  • Huang Huang
  • Xixi Chen
  • Tianmiao Huang
  • Wenli Li
  • Yubo LiuEmail author
  • Jianing ZhangEmail author
Original Article
First Online:
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Abstract

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 β-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.

Keywords

Caveolin-1 Rfng MAPK Hnf4a Sp1 HCC 
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Notes

Supplementary material

13105_2019_703_MOESM1_ESM.xlsx (575 kb)
ESM 1 (XLSX 574 kb)

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Copyright information

© University of Navarra 2019

Authors and Affiliations

  1. 1.School of Life Science and MedicineDalian University of TechnologyPanjinChina
  2. 2.School of Life Science and BiotechnologyDalian University of TechnologyDalianChina

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