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Gamma synuclein promotes cancer metastasis through the MKK3/6-p38MAPK cascade
Gamma synuclein (SNCG) is a neuronal protein that is also aberrantly overexpressed in various types of human cancer. SNCG overexpression promotes cancer invasion and metastasis. However, the mechanisms that drive cancer metastasis upon SNCG expression remain elusive. Elucidation of the mechanisms un...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9134903/ https://www.ncbi.nlm.nih.gov/pubmed/35637967 http://dx.doi.org/10.7150/ijbs.69155 |
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author | Liu, Jieya Shao, Ting Zhang, Jin Liu, Qianyi Hua, Hui Zhang, Hongying Wang, Jiao Luo, Ting Shi, Yuenian Eric Jiang, Yangfu |
author_facet | Liu, Jieya Shao, Ting Zhang, Jin Liu, Qianyi Hua, Hui Zhang, Hongying Wang, Jiao Luo, Ting Shi, Yuenian Eric Jiang, Yangfu |
author_sort | Liu, Jieya |
collection | PubMed |
description | Gamma synuclein (SNCG) is a neuronal protein that is also aberrantly overexpressed in various types of human cancer. SNCG overexpression promotes cancer invasion and metastasis. However, the mechanisms that drive cancer metastasis upon SNCG expression remain elusive. Elucidation of the mechanisms underlying the promotion of cancer metastasis by SNCG may help discover therapeutic avenues for SNCG-overexpressed cancer. Here, we show that SNCG promotes transforming growth factor-β (TGF-β)-induced p38 mitogen-activated protein kinase (MAPK) phosphorylation. Mechanistically, SNCG promotes p38MAPK phosphorylation by interacting with the MAPK kinase 3/6 (MKK3/6) and prevents their degradation. SNCG knockdown leads to a decrease in TGF-β-induced phosphorylation of MKK3/6; and abrogates the induction of matrix metalloproteinase (MMP)-9 expression by TGF-β and its target gene Twist1. Furthermore, p38MAPK inhibition abrogates the promotion of MMP-9 expression and cancer cell invasion by SNCG. Both p38MAPK and MMP inhibitors can suppress the promotion of cancer cell invasion by SNCG. Finally, overexpression of SNCG in liver cancer cells promotes lung metastasis, which can be suppressed by the p38MAPK inhibitor. Together, our data uncover a previously unknown role of SNCG in promoting TGF-β-MKK3/6-p38MAPK signaling. This study highlights the critical role of p38MAPK in the promotion of cancer metastasis by SNCG, and indicates that p38MAPK inhibitor may serve as a potential therapeutic for SNCG-overexpressed cancer. |
format | Online Article Text |
id | pubmed-9134903 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-91349032022-05-29 Gamma synuclein promotes cancer metastasis through the MKK3/6-p38MAPK cascade Liu, Jieya Shao, Ting Zhang, Jin Liu, Qianyi Hua, Hui Zhang, Hongying Wang, Jiao Luo, Ting Shi, Yuenian Eric Jiang, Yangfu Int J Biol Sci Research Paper Gamma synuclein (SNCG) is a neuronal protein that is also aberrantly overexpressed in various types of human cancer. SNCG overexpression promotes cancer invasion and metastasis. However, the mechanisms that drive cancer metastasis upon SNCG expression remain elusive. Elucidation of the mechanisms underlying the promotion of cancer metastasis by SNCG may help discover therapeutic avenues for SNCG-overexpressed cancer. Here, we show that SNCG promotes transforming growth factor-β (TGF-β)-induced p38 mitogen-activated protein kinase (MAPK) phosphorylation. Mechanistically, SNCG promotes p38MAPK phosphorylation by interacting with the MAPK kinase 3/6 (MKK3/6) and prevents their degradation. SNCG knockdown leads to a decrease in TGF-β-induced phosphorylation of MKK3/6; and abrogates the induction of matrix metalloproteinase (MMP)-9 expression by TGF-β and its target gene Twist1. Furthermore, p38MAPK inhibition abrogates the promotion of MMP-9 expression and cancer cell invasion by SNCG. Both p38MAPK and MMP inhibitors can suppress the promotion of cancer cell invasion by SNCG. Finally, overexpression of SNCG in liver cancer cells promotes lung metastasis, which can be suppressed by the p38MAPK inhibitor. Together, our data uncover a previously unknown role of SNCG in promoting TGF-β-MKK3/6-p38MAPK signaling. This study highlights the critical role of p38MAPK in the promotion of cancer metastasis by SNCG, and indicates that p38MAPK inhibitor may serve as a potential therapeutic for SNCG-overexpressed cancer. Ivyspring International Publisher 2022-05-01 /pmc/articles/PMC9134903/ /pubmed/35637967 http://dx.doi.org/10.7150/ijbs.69155 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Liu, Jieya Shao, Ting Zhang, Jin Liu, Qianyi Hua, Hui Zhang, Hongying Wang, Jiao Luo, Ting Shi, Yuenian Eric Jiang, Yangfu Gamma synuclein promotes cancer metastasis through the MKK3/6-p38MAPK cascade |
title | Gamma synuclein promotes cancer metastasis through the MKK3/6-p38MAPK cascade |
title_full | Gamma synuclein promotes cancer metastasis through the MKK3/6-p38MAPK cascade |
title_fullStr | Gamma synuclein promotes cancer metastasis through the MKK3/6-p38MAPK cascade |
title_full_unstemmed | Gamma synuclein promotes cancer metastasis through the MKK3/6-p38MAPK cascade |
title_short | Gamma synuclein promotes cancer metastasis through the MKK3/6-p38MAPK cascade |
title_sort | gamma synuclein promotes cancer metastasis through the mkk3/6-p38mapk cascade |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9134903/ https://www.ncbi.nlm.nih.gov/pubmed/35637967 http://dx.doi.org/10.7150/ijbs.69155 |
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