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PMID: 31209283 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

Caveolin-1 promotes invasion and metastasis by upregulating Pofut1 expression in mouse hepatocellular carcinoma.

Cell death & disease ·Vol. 10 ·No. 7 ·2019-00-17 ·Pages 477

Zhang C, Huang H, Zhang J, Wu Q, Chen X, Huang T, Li W, Liu Y, Zhang J

Abstract

Caveolin-1 (Cav-1) is an important structural protein of caveolae and plays an oncogene-like role by influencing protein glycosylation in hepatocellular carcinoma (HCC) cells. However, the mechanism by which Cav-1 promotes invasion and metastasis capacity has not been completely clarified. In this study, we demonstrate that Pofut1 is a fucosyltransferase induced by Cav-1. Mouse Hepa1-6 HCC cells lacking Cav-1 expression exhibited low transcription levels of Pofut1, whereas strong Pofut1 expression was found in high-metastasis-potential Hca-F cells with high levels of Cav-1. Cav-1 activated MAPK signaling and promoted phosphorylation of the transcription factors CREB, Sp1, HNF4A and c-Myc, which bound to the Pofut1 promoter region to induce its transcription. As Notch signaling receptors can be modified with O-fucose by Pofut1, we further showed that Cav-1-induced upregulation of Pofut1 expression activated the Notch pathway and thus enhanced invasion and metastasis by mouse HCC cells in vitro and in vivo. Collectively, our findings reveal a novel mechanism by which Cav-1 promotes tumor metastasis by upregulating expression of Pofut1, suggesting that Cav-1 may function as a new biomarker for HCC.

MeSH Terms
Animals Blotting, Western Carcinoma, Hepatocellular/genetics,metabolism,therapy Caveolin 1/genetics,metabolism,physiology Cell Line, Tumor Chromatin Immunoprecipitation Fucosyltransferases/genetics,metabolism Gene Expression Regulation, Neoplastic/genetics,physiology Immunohistochemistry Liver Neoplasms/genetics,metabolism,therapy Mice Phosphorylation/genetics,physiology Real-Time Polymerase Chain Reaction Signal Transduction/genetics,physiology
Chemicals
Caveolin 1 Fucosyltransferases Pofut1 protein, mouse
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Zhang Cheng
School of Life Science & Medicine, Dalian University of Technology, Panjin, China.
Huang Huang
School of Life Science & Medicine, Dalian University of Technology, Panjin, China.
Zhang Junshi
School of Life Science & Medicine, Dalian University of Technology, Panjin, China.
Wu Qiong
School of Life Science & Medicine, Dalian University of Technology, Panjin, China.
Chen Xixi
School of Life Science & Medicine, Dalian University of Technology, Panjin, China.
Huang Tianmiao
School of Life Science & Medicine, Dalian University of Technology, Panjin, China.
Li Wenli
School of Life Science & Medicine, Dalian University of Technology, Panjin, China. | School of Life Science & Biotechnology, Dalian University of Technology, Dalian, China.
Liu Yubo
School of Life Science & Medicine, Dalian University of Technology, Panjin, China. liuyubo@dlut.edu.cn.
Zhang Jianing
School of Life Science & Medicine, Dalian University of Technology, Panjin, China. jnzhang@dlut.edu.cn.
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Article Info
Journal
Cell death & disease
Abbr.
Cell Death Dis
ISSN
2041-4889
DOI
10.1038/s41419-019-1703-1
Email
liuyubo@dlut.edu.cn
jnzhang@dlut.edu.cn
Published
2019-00-17
Epub
2019-00-17
Pages
477
Language
English
Region
England
NLM ID
101524092
PMCID
PMC6572835
Subset
IM
Corrections
ErratumIn
PMID: 31358729
External Links
PubMed source DOI: 10.1038/s41419-019-1703-1 PMC Full Text View journal details
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