Cargando…
Caveolin-1 promotes invasion and metastasis by upregulating Pofut1 expression in mouse hepatocellular carcinoma
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 s...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572835/ https://www.ncbi.nlm.nih.gov/pubmed/31209283 http://dx.doi.org/10.1038/s41419-019-1703-1 |
_version_ | 1783427728248143872 |
---|---|
author | Zhang, Cheng Huang, Huang Zhang, Junshi Wu, Qiong Chen, Xixi Huang, Tianmiao Li, Wenli Liu, Yubo Zhang, Jianing |
author_facet | Zhang, Cheng Huang, Huang Zhang, Junshi Wu, Qiong Chen, Xixi Huang, Tianmiao Li, Wenli Liu, Yubo Zhang, Jianing |
author_sort | Zhang, Cheng |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6572835 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-65728352019-06-21 Caveolin-1 promotes invasion and metastasis by upregulating Pofut1 expression in mouse hepatocellular carcinoma Zhang, Cheng Huang, Huang Zhang, Junshi Wu, Qiong Chen, Xixi Huang, Tianmiao Li, Wenli Liu, Yubo Zhang, Jianing Cell Death Dis Article 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. Nature Publishing Group UK 2019-06-17 /pmc/articles/PMC6572835/ /pubmed/31209283 http://dx.doi.org/10.1038/s41419-019-1703-1 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Zhang, Cheng Huang, Huang Zhang, Junshi Wu, Qiong Chen, Xixi Huang, Tianmiao Li, Wenli Liu, Yubo Zhang, Jianing Caveolin-1 promotes invasion and metastasis by upregulating Pofut1 expression in mouse hepatocellular carcinoma |
title | Caveolin-1 promotes invasion and metastasis by upregulating Pofut1 expression in mouse hepatocellular carcinoma |
title_full | Caveolin-1 promotes invasion and metastasis by upregulating Pofut1 expression in mouse hepatocellular carcinoma |
title_fullStr | Caveolin-1 promotes invasion and metastasis by upregulating Pofut1 expression in mouse hepatocellular carcinoma |
title_full_unstemmed | Caveolin-1 promotes invasion and metastasis by upregulating Pofut1 expression in mouse hepatocellular carcinoma |
title_short | Caveolin-1 promotes invasion and metastasis by upregulating Pofut1 expression in mouse hepatocellular carcinoma |
title_sort | caveolin-1 promotes invasion and metastasis by upregulating pofut1 expression in mouse hepatocellular carcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572835/ https://www.ncbi.nlm.nih.gov/pubmed/31209283 http://dx.doi.org/10.1038/s41419-019-1703-1 |
work_keys_str_mv | AT zhangcheng caveolin1promotesinvasionandmetastasisbyupregulatingpofut1expressioninmousehepatocellularcarcinoma AT huanghuang caveolin1promotesinvasionandmetastasisbyupregulatingpofut1expressioninmousehepatocellularcarcinoma AT zhangjunshi caveolin1promotesinvasionandmetastasisbyupregulatingpofut1expressioninmousehepatocellularcarcinoma AT wuqiong caveolin1promotesinvasionandmetastasisbyupregulatingpofut1expressioninmousehepatocellularcarcinoma AT chenxixi caveolin1promotesinvasionandmetastasisbyupregulatingpofut1expressioninmousehepatocellularcarcinoma AT huangtianmiao caveolin1promotesinvasionandmetastasisbyupregulatingpofut1expressioninmousehepatocellularcarcinoma AT liwenli caveolin1promotesinvasionandmetastasisbyupregulatingpofut1expressioninmousehepatocellularcarcinoma AT liuyubo caveolin1promotesinvasionandmetastasisbyupregulatingpofut1expressioninmousehepatocellularcarcinoma AT zhangjianing caveolin1promotesinvasionandmetastasisbyupregulatingpofut1expressioninmousehepatocellularcarcinoma |