Pleiotropy of PP2A Phosphatases in Cancer with a Focus on Glioblastoma <i>IDH</i> Wildtype
Serine/Threonine protein phosphatase 2A (PP2A) is a heterotrimeric (or occasionally, heterodimeric) phosphatase with pleiotropic functions and ubiquitous expression. Despite the fact that they all contribute to protein dephosphorylation, multiple PP2A complexes exist which differ considerably by the...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/21/5227 |
| _version_ | 1797468884154974208 |
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| author | Elham Kashani Erik Vassella |
| author_facet | Elham Kashani Erik Vassella |
| author_sort | Elham Kashani |
| collection | DOAJ |
| description | Serine/Threonine protein phosphatase 2A (PP2A) is a heterotrimeric (or occasionally, heterodimeric) phosphatase with pleiotropic functions and ubiquitous expression. Despite the fact that they all contribute to protein dephosphorylation, multiple PP2A complexes exist which differ considerably by their subcellular localization and their substrate specificity, suggesting diverse PP2A functions. PP2A complex formation is tightly regulated by means of gene expression regulation by transcription factors, microRNAs, and post-translational modifications. Furthermore, a constant competition between PP2A regulatory subunits is taking place dynamically and depending on the spatiotemporal circumstance; many of the integral subunits can outcompete the rest, subjecting them to proteolysis. PP2A modulation is especially important in the context of brain tumors due to its ability to modulate distinct glioma-promoting signal transduction pathways, such as PI3K/Akt, Wnt, Ras, NF-κb, etc. Furthermore, PP2A is also implicated in DNA repair and survival pathways that are activated upon treatment of glioma cells with chemo-radiation. Depending on the cancer cell type, preclinical studies have shown some promise in utilising PP2A activator or PP2A inhibitors to overcome therapy resistance. This review has a special focus on “glioblastoma, IDH wild-type” (GBM) tumors, for which the therapy options have limited efficacy, and tumor relapse is inevitable. |
| first_indexed | 2024-03-09T19:13:40Z |
| format | Article |
| id | doaj.art-d35eecca451541c5b0ff1735b0420c68 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T19:13:40Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-d35eecca451541c5b0ff1735b0420c682023-11-24T04:01:06ZengMDPI AGCancers2072-66942022-10-011421522710.3390/cancers14215227Pleiotropy of PP2A Phosphatases in Cancer with a Focus on Glioblastoma <i>IDH</i> WildtypeElham Kashani0Erik Vassella1Institute of Pathology, University of Bern, 3008 Bern, SwitzerlandInstitute of Pathology, University of Bern, 3008 Bern, SwitzerlandSerine/Threonine protein phosphatase 2A (PP2A) is a heterotrimeric (or occasionally, heterodimeric) phosphatase with pleiotropic functions and ubiquitous expression. Despite the fact that they all contribute to protein dephosphorylation, multiple PP2A complexes exist which differ considerably by their subcellular localization and their substrate specificity, suggesting diverse PP2A functions. PP2A complex formation is tightly regulated by means of gene expression regulation by transcription factors, microRNAs, and post-translational modifications. Furthermore, a constant competition between PP2A regulatory subunits is taking place dynamically and depending on the spatiotemporal circumstance; many of the integral subunits can outcompete the rest, subjecting them to proteolysis. PP2A modulation is especially important in the context of brain tumors due to its ability to modulate distinct glioma-promoting signal transduction pathways, such as PI3K/Akt, Wnt, Ras, NF-κb, etc. Furthermore, PP2A is also implicated in DNA repair and survival pathways that are activated upon treatment of glioma cells with chemo-radiation. Depending on the cancer cell type, preclinical studies have shown some promise in utilising PP2A activator or PP2A inhibitors to overcome therapy resistance. This review has a special focus on “glioblastoma, IDH wild-type” (GBM) tumors, for which the therapy options have limited efficacy, and tumor relapse is inevitable.https://www.mdpi.com/2072-6694/14/21/5227Ser/Thr phosphatasesignaling pathwaybrain tumorsglioblastomatherapy |
| spellingShingle | Elham Kashani Erik Vassella Pleiotropy of PP2A Phosphatases in Cancer with a Focus on Glioblastoma <i>IDH</i> Wildtype Cancers Ser/Thr phosphatase signaling pathway brain tumors glioblastoma therapy |
| title | Pleiotropy of PP2A Phosphatases in Cancer with a Focus on Glioblastoma <i>IDH</i> Wildtype |
| title_full | Pleiotropy of PP2A Phosphatases in Cancer with a Focus on Glioblastoma <i>IDH</i> Wildtype |
| title_fullStr | Pleiotropy of PP2A Phosphatases in Cancer with a Focus on Glioblastoma <i>IDH</i> Wildtype |
| title_full_unstemmed | Pleiotropy of PP2A Phosphatases in Cancer with a Focus on Glioblastoma <i>IDH</i> Wildtype |
| title_short | Pleiotropy of PP2A Phosphatases in Cancer with a Focus on Glioblastoma <i>IDH</i> Wildtype |
| title_sort | pleiotropy of pp2a phosphatases in cancer with a focus on glioblastoma i idh i wildtype |
| topic | Ser/Thr phosphatase signaling pathway brain tumors glioblastoma therapy |
| url | https://www.mdpi.com/2072-6694/14/21/5227 |
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