Pleiotropy of PP2A Phosphatases in Cancer with a Focus on Glioblastoma IDH Wildtype.

Kashani, Elham; Vassella, Erik (2022). Pleiotropy of PP2A Phosphatases in Cancer with a Focus on Glioblastoma IDH Wildtype. Cancers, 14(21) MDPI AG 10.3390/cancers14215227

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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.

Item Type:

Journal Article (Review Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Tumour Pathology

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Kashani, Elham and Vassella, Erik

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2072-6694

Publisher:

MDPI AG

Language:

English

Submitter:

Pubmed Import

Date Deposited:

17 Nov 2022 13:32

Last Modified:

05 Dec 2022 16:28

Publisher DOI:

10.3390/cancers14215227

PubMed ID:

36358647

Uncontrolled Keywords:

Ser/Thr phosphatase brain tumors glioblastoma signaling pathway therapy

BORIS DOI:

10.48350/174769

URI:

https://boris.unibe.ch/id/eprint/174769

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