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Pard3 suppresses glioma invasion by regulating RhoA through atypical protein kinase C/NF‐κB signaling
Partitioning defective protein 3 (Pard3) has been reported to inhibit the progression of numerous human cancer cell types. However, the role of Pard3 in glioma progression remains unclear. In this study, the expression of Pard3 was measured in human gliomas of different grades by both quantitative p...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6536976/ https://www.ncbi.nlm.nih.gov/pubmed/30848088 http://dx.doi.org/10.1002/cam4.2063 |
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author | Li, Junjun Xu, Hao Wang, Qiangping Fu, Peng Huang, Tao Anas, Omarkhalil Zhao, Hongyang Xiong, Nanxiang |
author_facet | Li, Junjun Xu, Hao Wang, Qiangping Fu, Peng Huang, Tao Anas, Omarkhalil Zhao, Hongyang Xiong, Nanxiang |
author_sort | Li, Junjun |
collection | PubMed |
description | Partitioning defective protein 3 (Pard3) has been reported to inhibit the progression of numerous human cancer cell types. However, the role of Pard3 in glioma progression remains unclear. In this study, the expression of Pard3 was measured in human gliomas of different grades by both quantitative polymerase chain reaction and Western blotting. The effect of Pard3 on glioma progression was tested using cell counting kit‐8 assays, EdU assays, colony formation assays, cell migration, and invasion assays and tumor xenografts. The effect of Pard3 on Ras homolog family member A (RhoA) protein levels, subcellular localization, and transcriptional activity was measured by immunoblotting and immunofluorescence. Our results indicate that Pard3 functions as a tumor suppressor in gliomas and that the loss of Pard3 protein is strongly associated with a higher grade and poorer outcome. Pard3 overexpression inhibits glioma progression by upregulating RhoA protein levels. However, the level of GTP‐RhoA protein remained unchanged. Further evidence demonstrates that Pard3 regulates RhoA protein levels, subcellular localization and transcriptional activity by activating atypical protein kinase C/NF‐κB signaling. Mouse modeling experiments show that Pard3 overexpression inhibits glioma cell growth in vivo. Taken together, these findings identify RhoA as a novel target of Pard3 in gliomas and substantiate a novel regulatory role for Pard3 in glioma progression. This study reveals that Pard3 plays an inhibitory role in gliomas by regulating RhoA, which reveals a potential benefit for Pard3 activators in the prevention and therapy of gliomas. |
format | Online Article Text |
id | pubmed-6536976 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-65369762019-06-03 Pard3 suppresses glioma invasion by regulating RhoA through atypical protein kinase C/NF‐κB signaling Li, Junjun Xu, Hao Wang, Qiangping Fu, Peng Huang, Tao Anas, Omarkhalil Zhao, Hongyang Xiong, Nanxiang Cancer Med Cancer Biology Partitioning defective protein 3 (Pard3) has been reported to inhibit the progression of numerous human cancer cell types. However, the role of Pard3 in glioma progression remains unclear. In this study, the expression of Pard3 was measured in human gliomas of different grades by both quantitative polymerase chain reaction and Western blotting. The effect of Pard3 on glioma progression was tested using cell counting kit‐8 assays, EdU assays, colony formation assays, cell migration, and invasion assays and tumor xenografts. The effect of Pard3 on Ras homolog family member A (RhoA) protein levels, subcellular localization, and transcriptional activity was measured by immunoblotting and immunofluorescence. Our results indicate that Pard3 functions as a tumor suppressor in gliomas and that the loss of Pard3 protein is strongly associated with a higher grade and poorer outcome. Pard3 overexpression inhibits glioma progression by upregulating RhoA protein levels. However, the level of GTP‐RhoA protein remained unchanged. Further evidence demonstrates that Pard3 regulates RhoA protein levels, subcellular localization and transcriptional activity by activating atypical protein kinase C/NF‐κB signaling. Mouse modeling experiments show that Pard3 overexpression inhibits glioma cell growth in vivo. Taken together, these findings identify RhoA as a novel target of Pard3 in gliomas and substantiate a novel regulatory role for Pard3 in glioma progression. This study reveals that Pard3 plays an inhibitory role in gliomas by regulating RhoA, which reveals a potential benefit for Pard3 activators in the prevention and therapy of gliomas. John Wiley and Sons Inc. 2019-03-07 /pmc/articles/PMC6536976/ /pubmed/30848088 http://dx.doi.org/10.1002/cam4.2063 Text en © 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Cancer Biology Li, Junjun Xu, Hao Wang, Qiangping Fu, Peng Huang, Tao Anas, Omarkhalil Zhao, Hongyang Xiong, Nanxiang Pard3 suppresses glioma invasion by regulating RhoA through atypical protein kinase C/NF‐κB signaling |
title | Pard3 suppresses glioma invasion by regulating RhoA through atypical protein kinase C/NF‐κB signaling |
title_full | Pard3 suppresses glioma invasion by regulating RhoA through atypical protein kinase C/NF‐κB signaling |
title_fullStr | Pard3 suppresses glioma invasion by regulating RhoA through atypical protein kinase C/NF‐κB signaling |
title_full_unstemmed | Pard3 suppresses glioma invasion by regulating RhoA through atypical protein kinase C/NF‐κB signaling |
title_short | Pard3 suppresses glioma invasion by regulating RhoA through atypical protein kinase C/NF‐κB signaling |
title_sort | pard3 suppresses glioma invasion by regulating rhoa through atypical protein kinase c/nf‐κb signaling |
topic | Cancer Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6536976/ https://www.ncbi.nlm.nih.gov/pubmed/30848088 http://dx.doi.org/10.1002/cam4.2063 |
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