PP2A as a potential therapeutic target for breast cancer: Current insights and future perspectives - 22/03/24
Abstract |
Breast cancer has become the most prevalent malignancy worldwide; however, therapeutic efficacy is far from satisfactory. To alleviate the burden of this disease, it is imperative to discover novel mechanisms and treatment strategies. Protein phosphatase 2 A (PP2A) comprises a family of mammalian serine/threonine phosphatases that regulate many cellular processes. PP2A is dysregulated in several human diseases, including oncological pathologies, and plays a pivotal role in the initiation and progression of tumours. The role of PP2A as a tumour suppressor has been extensively studied, and its regulation can serve as a target for anticancer therapy. Recent studies have shown that PP2A is a tumour promotor. PP2A-mediated anticancer therapy may involve two opposing mechanisms: activation and inhibition. In general, the contradictory roles of PP2A should not be overlooked, and more work is needed to determine the molecular mechanism by which PP2A affects in tumours. In this review, the literature on the role of PP2A in tumours, especially in breast cancer, was analysed. This review describes relevant targets of breast cancer, such as cell cycle control, DNA damage responses, epidermal growth factor receptor, immune modulation and cell death resistance, which may lead to effective therapeutic strategies or influence drug development in breast cancer.
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This review introduces the subunits of PP2A, followed by an elucidation of the mechanisms through which PP2A inhibits tumour development. These mechanisms encompass the regulation of the cell cycle, inhibition of cancer stem cells, promotion of tumour cell apoptosis, and inhibition of tumour metastasis. Simultaneously, it provides a detailed exposition of the mechanisms through which PP2A facilitates tumour progression. Finally, the review also discusses the mechanisms of PP2A's synergistic effects in combination with chemotherapy, radiotherapy, targeted therapy, endocrine therapy, and immunotherapy, comprehensively presenting the multifaceted relationship between PP2A and tumours.
This review introduces the subunits of PP2A, followed by an elucidation of the mechanisms through which PP2A inhibits tumour development. These mechanisms encompass the regulation of the cell cycle, inhibition of cancer stem cells, promotion of tumour cell apoptosis, and inhibition of tumour metastasis. Simultaneously, it provides a detailed exposition of the mechanisms through which PP2A facilitates tumour progression. Finally, the review also discusses the mechanisms of PP2A's synergistic effects in combination with chemotherapy, radiotherapy, targeted therapy, endocrine therapy, and immunotherapy, comprehensively presenting the multifaceted relationship between PP2A and tumours.Le texte complet de cet article est disponible en PDF.
Abbreviations : PP2A, CSC, CDK1, CDK2, MASTL/Greatwall, ARPP19, ENSA, PKA, SphK1, S1PR3, STAT1, MPTP, ERK, TNBC, GSK3, NNMT, ABCA1, EMT, HRR, PARPi, TILs, CIP2A, TAM, DMFS, RFS, OS, Tregs, TMB, MSI
Keywords : Protein phosphatase 2 A, Breast cancer, Dephosphorylation, PP2A inhibitor, PP2A activator
Plan
Vol 173
Article 116398- avril 2024 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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