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TRIM56 acts through the IQGAP1-CDC42 signaling axis to promote glioma cell migration and invasion
Diffuse invasion is an important factor leading to treatment resistance and a poor prognosis in gliomas. Herein, we found that expression of the tripartite motif containing 56 (TRIM56), a RING-finger domain containing E3 ubiquitin ligase, was markedly higher in glioma than in normal brain tissue, an...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9985612/ https://www.ncbi.nlm.nih.gov/pubmed/36870986 http://dx.doi.org/10.1038/s41419-023-05702-6 |
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author | Zhang, Qing Zheng, Jianglin Wu, Wenjie Lian, Haiyan Iranzad, Natasha Wang, Endi Yang, Lianhe Wang, Xuan Jiang, Xiaobing |
author_facet | Zhang, Qing Zheng, Jianglin Wu, Wenjie Lian, Haiyan Iranzad, Natasha Wang, Endi Yang, Lianhe Wang, Xuan Jiang, Xiaobing |
author_sort | Zhang, Qing |
collection | PubMed |
description | Diffuse invasion is an important factor leading to treatment resistance and a poor prognosis in gliomas. Herein, we found that expression of the tripartite motif containing 56 (TRIM56), a RING-finger domain containing E3 ubiquitin ligase, was markedly higher in glioma than in normal brain tissue, and was significantly correlated with malignant phenotypes and a poor prognosis. In vitro and in vivo experimental studies revealed that TRIM56 promoted the migration and invasion of glioma cells. Mechanistically, TRIM56 was transcriptionally regulated by SP1 and promoted the K48-K63-linked poly-ubiquitination transition of IQGAP1 at Lys-1230 by interacting with it, which in turn promoted CDC42 activation. This mechanism was confirmed to mediate glioma migration and invasion. In conclusion, our study provides insights into the mechanisms through which TRIM56 promotes glioma motility, i.e., by regulating IQGAP1 ubiquitination to promote CDC42 activation, which might be clinically targeted for the treatment of glioma. |
format | Online Article Text |
id | pubmed-9985612 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-99856122023-03-06 TRIM56 acts through the IQGAP1-CDC42 signaling axis to promote glioma cell migration and invasion Zhang, Qing Zheng, Jianglin Wu, Wenjie Lian, Haiyan Iranzad, Natasha Wang, Endi Yang, Lianhe Wang, Xuan Jiang, Xiaobing Cell Death Dis Article Diffuse invasion is an important factor leading to treatment resistance and a poor prognosis in gliomas. Herein, we found that expression of the tripartite motif containing 56 (TRIM56), a RING-finger domain containing E3 ubiquitin ligase, was markedly higher in glioma than in normal brain tissue, and was significantly correlated with malignant phenotypes and a poor prognosis. In vitro and in vivo experimental studies revealed that TRIM56 promoted the migration and invasion of glioma cells. Mechanistically, TRIM56 was transcriptionally regulated by SP1 and promoted the K48-K63-linked poly-ubiquitination transition of IQGAP1 at Lys-1230 by interacting with it, which in turn promoted CDC42 activation. This mechanism was confirmed to mediate glioma migration and invasion. In conclusion, our study provides insights into the mechanisms through which TRIM56 promotes glioma motility, i.e., by regulating IQGAP1 ubiquitination to promote CDC42 activation, which might be clinically targeted for the treatment of glioma. Nature Publishing Group UK 2023-03-04 /pmc/articles/PMC9985612/ /pubmed/36870986 http://dx.doi.org/10.1038/s41419-023-05702-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Zhang, Qing Zheng, Jianglin Wu, Wenjie Lian, Haiyan Iranzad, Natasha Wang, Endi Yang, Lianhe Wang, Xuan Jiang, Xiaobing TRIM56 acts through the IQGAP1-CDC42 signaling axis to promote glioma cell migration and invasion |
title | TRIM56 acts through the IQGAP1-CDC42 signaling axis to promote glioma cell migration and invasion |
title_full | TRIM56 acts through the IQGAP1-CDC42 signaling axis to promote glioma cell migration and invasion |
title_fullStr | TRIM56 acts through the IQGAP1-CDC42 signaling axis to promote glioma cell migration and invasion |
title_full_unstemmed | TRIM56 acts through the IQGAP1-CDC42 signaling axis to promote glioma cell migration and invasion |
title_short | TRIM56 acts through the IQGAP1-CDC42 signaling axis to promote glioma cell migration and invasion |
title_sort | trim56 acts through the iqgap1-cdc42 signaling axis to promote glioma cell migration and invasion |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9985612/ https://www.ncbi.nlm.nih.gov/pubmed/36870986 http://dx.doi.org/10.1038/s41419-023-05702-6 |
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