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Involvement of Phosphatase and Tensin Homolog in Cyclin-Dependent Kinase 4/6 Inhibitor-Induced Blockade of Glioblastoma
Dysregulation of retinoblastoma (Rb) signaling pathway have been established as a requirement for glioblastoma (GBM) initiation and progression, which suggests that blockade of CDK4/6-Rb signaling axis for GBM treatment. Palbociclib, a selective inhibitor of the cyclin-dependent kinases CDK4/6, has...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854038/ https://www.ncbi.nlm.nih.gov/pubmed/31787897 http://dx.doi.org/10.3389/fphar.2019.01316 |
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author | Liu, Songlin Yuan, Dun Li, Yifeng Qi, Qi Guo, Bingzhong Yang, Shun Zhou, Jilin Xu, Lu Chen, Tiange Yang, Chenxing Liu, Junyu Li, Buyan Yao, Li Jiang, Weixi |
author_facet | Liu, Songlin Yuan, Dun Li, Yifeng Qi, Qi Guo, Bingzhong Yang, Shun Zhou, Jilin Xu, Lu Chen, Tiange Yang, Chenxing Liu, Junyu Li, Buyan Yao, Li Jiang, Weixi |
author_sort | Liu, Songlin |
collection | PubMed |
description | Dysregulation of retinoblastoma (Rb) signaling pathway have been established as a requirement for glioblastoma (GBM) initiation and progression, which suggests that blockade of CDK4/6-Rb signaling axis for GBM treatment. Palbociclib, a selective inhibitor of the cyclin-dependent kinases CDK4/6, has been applied for breast cancer treatment. However, its efficacy against glioblastoma has not been well clarified. Here, effects of CDK4/6 inhibitors on various kinds of GBM cell lines are investigated and the functional mechanisms are identified. Data showed that cells with diverse PTEN status respond to palbociclib differently. Gain-of-function and loss-of-function studies indicated that PTEN enhanced the sensitivity of GBM cells to palbociclib in vitro and in vivo, which was associated with suppressions of Akt and ERK signaling and independent of Rb signaling inhibition. Hence, our findings support that palbociclib selectively |
format | Online Article Text |
id | pubmed-6854038 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-68540382019-11-29 Involvement of Phosphatase and Tensin Homolog in Cyclin-Dependent Kinase 4/6 Inhibitor-Induced Blockade of Glioblastoma Liu, Songlin Yuan, Dun Li, Yifeng Qi, Qi Guo, Bingzhong Yang, Shun Zhou, Jilin Xu, Lu Chen, Tiange Yang, Chenxing Liu, Junyu Li, Buyan Yao, Li Jiang, Weixi Front Pharmacol Pharmacology Dysregulation of retinoblastoma (Rb) signaling pathway have been established as a requirement for glioblastoma (GBM) initiation and progression, which suggests that blockade of CDK4/6-Rb signaling axis for GBM treatment. Palbociclib, a selective inhibitor of the cyclin-dependent kinases CDK4/6, has been applied for breast cancer treatment. However, its efficacy against glioblastoma has not been well clarified. Here, effects of CDK4/6 inhibitors on various kinds of GBM cell lines are investigated and the functional mechanisms are identified. Data showed that cells with diverse PTEN status respond to palbociclib differently. Gain-of-function and loss-of-function studies indicated that PTEN enhanced the sensitivity of GBM cells to palbociclib in vitro and in vivo, which was associated with suppressions of Akt and ERK signaling and independent of Rb signaling inhibition. Hence, our findings support that palbociclib selectively Frontiers Media S.A. 2019-11-07 /pmc/articles/PMC6854038/ /pubmed/31787897 http://dx.doi.org/10.3389/fphar.2019.01316 Text en Copyright © 2019 Liu, Yuan, Li, Qi, Guo, Yang, Zhou, Xu, Chen, Yang, Liu, Li, Yao and Jiang http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Liu, Songlin Yuan, Dun Li, Yifeng Qi, Qi Guo, Bingzhong Yang, Shun Zhou, Jilin Xu, Lu Chen, Tiange Yang, Chenxing Liu, Junyu Li, Buyan Yao, Li Jiang, Weixi Involvement of Phosphatase and Tensin Homolog in Cyclin-Dependent Kinase 4/6 Inhibitor-Induced Blockade of Glioblastoma |
title | Involvement of Phosphatase and Tensin Homolog in Cyclin-Dependent Kinase 4/6 Inhibitor-Induced Blockade of Glioblastoma |
title_full | Involvement of Phosphatase and Tensin Homolog in Cyclin-Dependent Kinase 4/6 Inhibitor-Induced Blockade of Glioblastoma |
title_fullStr | Involvement of Phosphatase and Tensin Homolog in Cyclin-Dependent Kinase 4/6 Inhibitor-Induced Blockade of Glioblastoma |
title_full_unstemmed | Involvement of Phosphatase and Tensin Homolog in Cyclin-Dependent Kinase 4/6 Inhibitor-Induced Blockade of Glioblastoma |
title_short | Involvement of Phosphatase and Tensin Homolog in Cyclin-Dependent Kinase 4/6 Inhibitor-Induced Blockade of Glioblastoma |
title_sort | involvement of phosphatase and tensin homolog in cyclin-dependent kinase 4/6 inhibitor-induced blockade of glioblastoma |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854038/ https://www.ncbi.nlm.nih.gov/pubmed/31787897 http://dx.doi.org/10.3389/fphar.2019.01316 |
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