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Lung adenocarcinoma–derived vWF promotes tumor metastasis by regulating PHKG1‐mediated glycogen metabolism
Tumor metastasis is a series of complicated biological events. Hematogenous metastasis mediated by von Willebrand factor (vWF) is critical in tumor metastasis. However, the source of vWF and its role in tumor metastasis are controversial, and the further mechanism involved in mediating tumor metasta...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8990721/ https://www.ncbi.nlm.nih.gov/pubmed/35150045 http://dx.doi.org/10.1111/cas.15298 |
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author | Gu, Jiayi Qi, Yingxue Lu, Yuxin Tao, Qianying Yu, Die Jiang, Chunchun Liu, Jianwen Liang, Xin |
author_facet | Gu, Jiayi Qi, Yingxue Lu, Yuxin Tao, Qianying Yu, Die Jiang, Chunchun Liu, Jianwen Liang, Xin |
author_sort | Gu, Jiayi |
collection | PubMed |
description | Tumor metastasis is a series of complicated biological events. Hematogenous metastasis mediated by von Willebrand factor (vWF) is critical in tumor metastasis. However, the source of vWF and its role in tumor metastasis are controversial, and the further mechanism involved in mediating tumor metastasis is still unclear. In this study, we first demonstrated that lung adenocarcinoma cells could express vWF de novo and promotes tumor metastasis. Through the analysis of transcriptome sequencing, the metastasis promotion effect of vWF may be related to phosphorylase kinase subunit G1 (PHKG1), a catalytic subtype of phosphorylase kinase (PhK). PHKG1 was highly expressed in lung adenocarcinoma patients and led to poor prognosis. Further experiments found that lung adenocarcinoma–derived vWF induced the upregulation of PHKG1 through the PI3K/AKT pathway to promote glycogenolysis. Glycogen was funneled into glycolysis, leading to increased metastasis. Tumor metastasis assayed in vitro and in vivo showed that knockdown of PHKG1 or synergistic injection of phosphorylase inhibition based on the overexpression of vWF could inhibit metastasis. In summary, our research proved that lung adenocarcinoma–derived vWF may mediate tumor metastasis by regulating PHKG1 to promote glycogen metabolism and suggested potential targets for inhibition of lung adenocarcinoma metastasis. |
format | Online Article Text |
id | pubmed-8990721 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-89907212022-04-13 Lung adenocarcinoma–derived vWF promotes tumor metastasis by regulating PHKG1‐mediated glycogen metabolism Gu, Jiayi Qi, Yingxue Lu, Yuxin Tao, Qianying Yu, Die Jiang, Chunchun Liu, Jianwen Liang, Xin Cancer Sci ORIGINAL ARTICLES Tumor metastasis is a series of complicated biological events. Hematogenous metastasis mediated by von Willebrand factor (vWF) is critical in tumor metastasis. However, the source of vWF and its role in tumor metastasis are controversial, and the further mechanism involved in mediating tumor metastasis is still unclear. In this study, we first demonstrated that lung adenocarcinoma cells could express vWF de novo and promotes tumor metastasis. Through the analysis of transcriptome sequencing, the metastasis promotion effect of vWF may be related to phosphorylase kinase subunit G1 (PHKG1), a catalytic subtype of phosphorylase kinase (PhK). PHKG1 was highly expressed in lung adenocarcinoma patients and led to poor prognosis. Further experiments found that lung adenocarcinoma–derived vWF induced the upregulation of PHKG1 through the PI3K/AKT pathway to promote glycogenolysis. Glycogen was funneled into glycolysis, leading to increased metastasis. Tumor metastasis assayed in vitro and in vivo showed that knockdown of PHKG1 or synergistic injection of phosphorylase inhibition based on the overexpression of vWF could inhibit metastasis. In summary, our research proved that lung adenocarcinoma–derived vWF may mediate tumor metastasis by regulating PHKG1 to promote glycogen metabolism and suggested potential targets for inhibition of lung adenocarcinoma metastasis. John Wiley and Sons Inc. 2022-02-20 2022-04 /pmc/articles/PMC8990721/ /pubmed/35150045 http://dx.doi.org/10.1111/cas.15298 Text en © 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | ORIGINAL ARTICLES Gu, Jiayi Qi, Yingxue Lu, Yuxin Tao, Qianying Yu, Die Jiang, Chunchun Liu, Jianwen Liang, Xin Lung adenocarcinoma–derived vWF promotes tumor metastasis by regulating PHKG1‐mediated glycogen metabolism |
title | Lung adenocarcinoma–derived vWF promotes tumor metastasis by regulating PHKG1‐mediated glycogen metabolism |
title_full | Lung adenocarcinoma–derived vWF promotes tumor metastasis by regulating PHKG1‐mediated glycogen metabolism |
title_fullStr | Lung adenocarcinoma–derived vWF promotes tumor metastasis by regulating PHKG1‐mediated glycogen metabolism |
title_full_unstemmed | Lung adenocarcinoma–derived vWF promotes tumor metastasis by regulating PHKG1‐mediated glycogen metabolism |
title_short | Lung adenocarcinoma–derived vWF promotes tumor metastasis by regulating PHKG1‐mediated glycogen metabolism |
title_sort | lung adenocarcinoma–derived vwf promotes tumor metastasis by regulating phkg1‐mediated glycogen metabolism |
topic | ORIGINAL ARTICLES |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8990721/ https://www.ncbi.nlm.nih.gov/pubmed/35150045 http://dx.doi.org/10.1111/cas.15298 |
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