Editorial

4 pages, 192 KiB

Open AccessEditorial

Protein Phosphorylation in Cancer: Unraveling the Signaling Pathways

by Peter Coopman

Biomolecules 2022, 12(8), 1036; https://doi.org/10.3390/biom12081036 - 27 Jul 2022

Cited by 2 | Viewed by 1169

The discovery of protein kinase playing key roles in cancer formation and progression has triggered great interest and stimulated intense research on signaling pathways to develop targeted treatments, as well as to identify prognostic and predictive biomarkers [...] Full article

(This article belongs to the Special Issue Protein Phosphorylation in Cancer: Unraveling the Signaling Pathways)

Research

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13 pages, 3524 KiB

Open AccessArticle

Phosphorylation of RCC1 on Serine 11 Facilitates G1/S Transition in HPV E7-Expressing Cells

by Xiaoyan Hou, Lijun Qiao, Ruijuan Liu, Xuechao Han and Weifang Zhang

Biomolecules 2021, 11(7), 995; https://doi.org/10.3390/biom11070995 - 06 Jul 2021

Cited by 5 | Viewed by 2186

Abstract

Persistent infection of high-risk human papillomavirus (HR-HPV) plays a causal role in cervical cancer. Regulator of chromosome condensation 1 (RCC1) is a critical cell cycle regulator, which undergoes a few post-translational modifications including phosphorylation. Here, we showed that serine 11 (S11) of RCC1 [...] Read more.

Persistent infection of high-risk human papillomavirus (HR-HPV) plays a causal role in cervical cancer. Regulator of chromosome condensation 1 (RCC1) is a critical cell cycle regulator, which undergoes a few post-translational modifications including phosphorylation. Here, we showed that serine 11 (S11) of RCC1 was phosphorylated in HPV E7-expressing cells. However, S11 phosphorylation was not up-regulated by CDK1 in E7-expressing cells; instead, the PI3K/AKT/mTOR pathway promoted S11 phosphorylation. Knockdown of AKT or inhibition of the PI3K/AKT/mTOR pathway down-regulated phosphorylation of RCC1 S11. Furthermore, S11 phosphorylation occurred throughout the cell cycle, and reached its peak during the mitosis phase. Our previous data proved that RCC1 was necessary for the G1/S cell cycle progression, and in the present study we showed that the RCC1 mutant, in which S11 was mutated to alanine (S11A) to mimic non-phosphorylation status, lost the ability to facilitate G1/S transition in E7-expressing cells. Moreover, RCC1 S11 was phosphorylated by the PI3K/AKT/mTOR pathway in HPV-positive cervical cancer SiHa and HeLa cells. We conclude that S11 of RCC1 is phosphorylated by the PI3K/AKT/mTOR pathway and phosphorylation of RCC1 S11 facilitates the abrogation of G1 checkpoint in HPV E7-expressing cells. In short, our study explores a new role of RCC1 S11 phosphorylation in cell cycle regulation. Full article

(This article belongs to the Special Issue Protein Phosphorylation in Cancer: Unraveling the Signaling Pathways)

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15 pages, 2817 KiB

Open AccessArticle

RET Regulates Human Medullary Thyroid Cancer Cell Proliferation through CDK5 and STAT3 Activation

by Chia-Herng Yue, Muhammet Oner, Chih-Yuan Chiu, Mei-Chih Chen, Chieh-Lin Teng, Hsin-Yi Wang, Jer-Tsong Hsieh, Chih-Ho Lai and Ho Lin

Biomolecules 2021, 11(6), 860; https://doi.org/10.3390/biom11060860 - 09 Jun 2021

Cited by 8 | Viewed by 3375

Abstract

Medullary thyroid cancer (MTC) is a neuroendocrine tumor that arises from the parafollicular C-cells, which produces the hormone calcitonin. RET is a transmembrane receptor protein-tyrosine kinase, which is highly expressed in MTC. Our previous studies reported that cyclin-dependent kinase 5 (CDK5) plays a [...] Read more.

Medullary thyroid cancer (MTC) is a neuroendocrine tumor that arises from the parafollicular C-cells, which produces the hormone calcitonin. RET is a transmembrane receptor protein-tyrosine kinase, which is highly expressed in MTC. Our previous studies reported that cyclin-dependent kinase 5 (CDK5) plays a crucial role in cancer progression, including MTC. However, the role of CDK5 in GDNF-induced RET signaling in medullary thyroid cancer proliferation remains unknown. Here, we investigated RET activation and its biochemically interaction with CDK5 in GDNF-induced medullary thyroid cancer proliferation. Our results demonstrated that GDNF stimulated RET phosphorylation and thus subsequently resulted in CDK5 activation by its phosphorylation. Activated CDK5 further caused STAT3 activation by its specific phosphorylation at Ser727. Moreover, we also found that GDNF treatment enhanced ERK1/2 and EGR1 activity, which is involved in p35 activation. Interestingly, we identified for the first time that CDK5 physically interacted with RET protein in MTC. Overall, our results provide a new mechanism for medullary thyroid cancer cell proliferation, suggesting that targeting CDK5 may be a promising therapeutic candidate for human medullary thyroid cancer in the near future. Full article

(This article belongs to the Special Issue Protein Phosphorylation in Cancer: Unraveling the Signaling Pathways)

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19 pages, 3936 KiB

Open AccessArticle

Comparison of SYK Signaling Networks Reveals the Potential Molecular Determinants of Its Tumor-Promoting and Suppressing Functions

by Marion Buffard, Aurélien Naldi, Gilles Freiss, Marcel Deckert, Ovidiu Radulescu, Peter J. Coopman and Romain M. Larive

Biomolecules 2021, 11(2), 308; https://doi.org/10.3390/biom11020308 - 18 Feb 2021

Cited by 4 | Viewed by 2756

Abstract

Spleen tyrosine kinase (SYK) can behave as an oncogene or a tumor suppressor, depending on the cell and tissue type. As pharmacological SYK inhibitors are currently evaluated in clinical trials, it is important to gain more information on the molecular mechanisms underpinning these [...] Read more.

Spleen tyrosine kinase (SYK) can behave as an oncogene or a tumor suppressor, depending on the cell and tissue type. As pharmacological SYK inhibitors are currently evaluated in clinical trials, it is important to gain more information on the molecular mechanisms underpinning these opposite roles. To this aim, we reconstructed and compared its signaling networks using phosphoproteomic data from breast cancer and Burkitt lymphoma cell lines where SYK behaves as a tumor suppressor and promoter. Bioinformatic analyses allowed for unveiling the main differences in signaling pathways, network topology and signal propagation from SYK to its potential effectors. In breast cancer cells, the SYK target-enriched signaling pathways included intercellular adhesion and Hippo signaling components that are often linked to tumor suppression. In Burkitt lymphoma cells, the SYK target-enriched signaling pathways included molecules that could play a role in SYK pro-oncogenic function in B-cell lymphomas. Several protein interactions were profoundly rewired in the breast cancer network compared with the Burkitt lymphoma network. These data demonstrate that proteomic profiling combined with mathematical network modeling allows untangling complex pathway interplays and revealing difficult to discern interactions among the SYK pathways that positively and negatively affect tumor formation and progression. Full article

(This article belongs to the Special Issue Protein Phosphorylation in Cancer: Unraveling the Signaling Pathways)

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14 pages, 3355 KiB

Open AccessArticle

The Cytotoxicity of RNase-Derived Peptides

by Vera Ulyanova, Elena Dudkina, Alsu Nadyrova, Vladimir Kalashnikov, Yulia Surchenko and Olga Ilinskaya

Biomolecules 2021, 11(1), 16; https://doi.org/10.3390/biom11010016 - 26 Dec 2020

Cited by 6 | Viewed by 2738

Abstract

Bacterial ribonuclease binase exhibits a cytotoxic effect on tumor cells possessing certain oncogenes. The aim of this study was to identify the structural parts of the binase molecule that exert cytotoxicity. Out of five designed peptides, the peptides representing the binase regions 21–50 [...] Read more.

Bacterial ribonuclease binase exhibits a cytotoxic effect on tumor cells possessing certain oncogenes. The aim of this study was to identify the structural parts of the binase molecule that exert cytotoxicity. Out of five designed peptides, the peptides representing the binase regions 21–50 and 74–94 have the highest cytotoxic potential toward human cervical HeLa and breast BT-20 and MCF-7 cancer cells. The peptides B21–50 and B74–94 were not able to enter human lung adenocarcinoma A549 cells, unlike BT-20 cells, explaining their failure to inhibit A549 cell proliferation. The peptide B74–94 shares similarities with epidermal growth factor (EGF), suggesting the peptide’s specificity for EGF receptor overexpressed in BT-20 cells. Thus, the binase-derived peptides have the potential of being further developed as tumor-targeting peptides. Full article

(This article belongs to the Special Issue Protein Phosphorylation in Cancer: Unraveling the Signaling Pathways)

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13 pages, 2608 KiB

Open AccessFeature PaperArticle

The Receptor Tyrosine Kinase TrkA Is Increased and Targetable in HER2-Positive Breast Cancer

by Nathan Griffin, Mark Marsland, Severine Roselli, Christopher Oldmeadow, John Attia, Marjorie M. Walker, Hubert Hondermarck and Sam Faulkner

Biomolecules 2020, 10(9), 1329; https://doi.org/10.3390/biom10091329 - 17 Sep 2020

Cited by 9 | Viewed by 3037

Abstract

The tyrosine kinase receptor A (NTRK1/TrkA) is increasingly regarded as a therapeutic target in oncology. In breast cancer, TrkA contributes to metastasis but the clinicopathological significance remains unclear. In this study, TrkA expression was assessed via immunohistochemistry of 158 invasive ductal carcinomas (IDC), [...] Read more.

The tyrosine kinase receptor A (NTRK1/TrkA) is increasingly regarded as a therapeutic target in oncology. In breast cancer, TrkA contributes to metastasis but the clinicopathological significance remains unclear. In this study, TrkA expression was assessed via immunohistochemistry of 158 invasive ductal carcinomas (IDC), 158 invasive lobular carcinomas (ILC) and 50 ductal carcinomas in situ (DCIS). TrkA was expressed in cancer epithelial and myoepithelial cells, with higher levels of TrkA positively associated with IDC (39% of cases) (p < 0.0001). Interestingly, TrkA was significantly increased in tumours expressing the human epidermal growth factor receptor-2 (HER2), with expression in 49% of HER2-positive compared to 25% of HER2-negative tumours (p = 0.0027). A panel of breast cancer cells were used to confirm TrkA protein expression, demonstrating higher levels of TrkA (total and phosphorylated) in HER2-positive cell lines. Functional investigations using four different HER2-positive breast cancer cell lines indicated that the Trk tyrosine kinase inhibitor GNF-5837 reduced cell viability, through decreased phospho-TrkA (Tyr490) and downstream AKT (Ser473) activation, but did not display synergy with Herceptin. Overall, these data highlight a relationship between the tyrosine kinase receptors TrkA and HER2 and suggest the potential of TrkA as a novel or adjunct target for HER2-positive breast tumours. Full article

(This article belongs to the Special Issue Protein Phosphorylation in Cancer: Unraveling the Signaling Pathways)

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17 pages, 4415 KiB

Open AccessArticle

Activated Protein Kinase C (PKC) Is Persistently Trafficked with Epidermal Growth Factor (EGF) Receptor

by Carol A. Heckman, Tania Biswas, Douglas M. Dimick and Marilyn L. Cayer

Biomolecules 2020, 10(9), 1288; https://doi.org/10.3390/biom10091288 - 07 Sep 2020

Cited by 4 | Viewed by 3600

Abstract

Protein kinase Cs (PKCs) are activated by lipids in the plasma membrane and bind to a scaffold assembled on the epidermal growth factor (EGF) receptor (EGFR). Understanding how this complex is routed is important, because this determines whether EGFR is degraded, terminating signaling. [...] Read more.

Protein kinase Cs (PKCs) are activated by lipids in the plasma membrane and bind to a scaffold assembled on the epidermal growth factor (EGF) receptor (EGFR). Understanding how this complex is routed is important, because this determines whether EGFR is degraded, terminating signaling. Here, cells were preincubated in EGF-tagged gold nanoparticles, then allowed to internalize them in the presence or absence of a phorbol ester PKC activator. PKC colocalized with EGF-tagged nanoparticles within 5 min and migrated with EGFR-bearing vesicles into the cell. Two conformations of PKC-epsilon were distinguished by different primary antibodies. One, thought to be enzymatically active, was on endosomes and displayed a binding site for antibody RR (R&D). The other, recognized by Genetex green (GG), was soluble, on actin-rich structures, and loosely bound to vesicles. During a 15-min chase, EGF-tagged nanoparticles entered large, perinuclear structures. In phorbol ester-treated cells, vesicles bearing EGF-tagged nanoparticles tended to enter this endocytic recycling compartment (ERC) without the GG form. The correlation coefficient between the GG (inactive) and RR conformations on vesicles was also lower. Thus, active PKC has a Charon-like function, ferrying vesicles to the ERC, and inactivation counteracts this function. The advantage conferred on cells by aggregating vesicles in the ERC is unclear. Full article

(This article belongs to the Special Issue Protein Phosphorylation in Cancer: Unraveling the Signaling Pathways)

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Review

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16 pages, 3437 KiB

Open AccessReview

Protein Phosphorylation in Cancer: Role of Nitric Oxide Signaling Pathway

by Xinran Liu, Yiping Zhang, Yijie Wang, Meiwen Yang, Fenfang Hong and Shulong Yang

Biomolecules 2021, 11(7), 1009; https://doi.org/10.3390/biom11071009 - 10 Jul 2021

Cited by 36 | Viewed by 4649

Abstract

Nitric oxide (NO), a free radical, plays a critical role in a wide range of physiological and pathological processes. Due to its pleiotropic function, it has been widely investigated in various types of cancers and is strongly associated with cancer development. Mounting pieces [...] Read more.

Nitric oxide (NO), a free radical, plays a critical role in a wide range of physiological and pathological processes. Due to its pleiotropic function, it has been widely investigated in various types of cancers and is strongly associated with cancer development. Mounting pieces of evidence show that NO regulates various cancer-related events, which mainly depends on phosphorylating the key proteins in several signaling pathways. However, phosphorylation of proteins modulated by NO signaling pathway may lead to different effects in different types of cancer, which is complex and remains unclear. Therefore, in this review, we focus on the effect of protein phosphorylation modulated by NO signaling pathway in different types of cancers including breast cancer, lung cancer, prostate cancer, colon cancer, gastric cancer, pancreatic cancer, ovarian cancer, and neuroblastoma. Phosphorylation of key proteins, including p38 MAPK, ERK, PI3K, STAT3, and p53, modified by NO in various signaling pathways affects different cancer-related processes including cell apoptosis, proliferation, angiogenesis, metastasis, and several cancer therapies. Our review links the NO signaling pathway to protein phosphorylation in cancer development and provides new insight into potential targets and cancer therapy. Full article

(This article belongs to the Special Issue Protein Phosphorylation in Cancer: Unraveling the Signaling Pathways)

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30 pages, 1984 KiB

Open AccessReview

Multifaceted Functions of Protein Kinase D in Pathological Processes and Human Diseases

by Xuejing Zhang, Jaclyn Connelly, Yapeng Chao and Qiming Jane Wang

Biomolecules 2021, 11(3), 483; https://doi.org/10.3390/biom11030483 - 23 Mar 2021

Cited by 27 | Viewed by 4842

Abstract

Protein kinase D (PKD) is a family of serine/threonine protein kinases operating in the signaling network of the second messenger diacylglycerol. The three family members, PKD1, PKD2, and PKD3, are activated by a variety of extracellular stimuli and transduce cell signals affecting many [...] Read more.

Protein kinase D (PKD) is a family of serine/threonine protein kinases operating in the signaling network of the second messenger diacylglycerol. The three family members, PKD1, PKD2, and PKD3, are activated by a variety of extracellular stimuli and transduce cell signals affecting many aspects of basic cell functions including secretion, migration, proliferation, survival, angiogenesis, and immune response. Dysregulation of PKD in expression and activity has been detected in many human diseases. Further loss- or gain-of-function studies at cellular levels and in animal models provide strong support for crucial roles of PKD in many pathological conditions, including cancer, metabolic disorders, cardiac diseases, central nervous system disorders, inflammatory diseases, and immune dysregulation. Complexity in enzymatic regulation and function is evident as PKD isoforms may act differently in different biological systems and disease models, and understanding the molecular mechanisms underlying these differences and their biological significance in vivo is essential for the development of safer and more effective PKD-targeted therapies. In this review, to provide a global understanding of PKD function, we present an overview of the PKD family in several major human diseases with more focus on cancer-associated biological processes. Full article

(This article belongs to the Special Issue Protein Phosphorylation in Cancer: Unraveling the Signaling Pathways)

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12 pages, 881 KiB

Open AccessReview

The Emerging Function of PKCtheta in Cancer

by Amandine Nicolle, Ye Zhang and Karine Belguise

Biomolecules 2021, 11(2), 221; https://doi.org/10.3390/biom11020221 - 05 Feb 2021

Cited by 16 | Viewed by 3538

Abstract

Protein Kinase C theta (PKCθ) is a serine/threonine kinase that belongs to the novel PKC subfamily. In normal tissue, its expression is restricted to skeletal muscle cells, platelets and T lymphocytes in which PKCθ controls several essential cellular processes such as survival, proliferation [...] Read more.

Protein Kinase C theta (PKCθ) is a serine/threonine kinase that belongs to the novel PKC subfamily. In normal tissue, its expression is restricted to skeletal muscle cells, platelets and T lymphocytes in which PKCθ controls several essential cellular processes such as survival, proliferation and differentiation. Particularly, PKCθ has been extensively studied for its role in the immune system where its translocation to the immunological synapse plays a critical role in T cell activation. Beyond its physiological role in immune responses, increasing evidence implicates PKCθ in the pathology of various diseases, especially autoimmune disorders and cancers. In this review, we discuss the implication of PKCθ in various types of cancers and the PKCθ-mediated signaling events controlling cancer initiation and progression. In these types of cancers, the high PKCθ expression leads to aberrant cell proliferation, migration and invasion resulting in malignant phenotype. The recent development and application of PKCθ inhibitors in the context of autoimmune diseases could benefit the emergence of treatment for cancers in which PKCθ has been implicated. Full article

(This article belongs to the Special Issue Protein Phosphorylation in Cancer: Unraveling the Signaling Pathways)

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13 pages, 1193 KiB

Open AccessReview

Phosphorylation of the Regulators, a Complex Facet of NF-κB Signaling in Cancer

by Aishat Motolani, Matthew Martin, Mengyao Sun and Tao Lu

Biomolecules 2021, 11(1), 15; https://doi.org/10.3390/biom11010015 - 26 Dec 2020

Cited by 23 | Viewed by 3951

Abstract

The nuclear factor kappa B (NF-κB) is a ubiquitous transcription factor central to inflammation and various malignant diseases in humans. The regulation of NF-κB can be influenced by a myriad of post-translational modifications (PTMs), including phosphorylation, one of the most popular PTM formats [...] Read more.

The nuclear factor kappa B (NF-κB) is a ubiquitous transcription factor central to inflammation and various malignant diseases in humans. The regulation of NF-κB can be influenced by a myriad of post-translational modifications (PTMs), including phosphorylation, one of the most popular PTM formats in NF-κB signaling. The regulation by phosphorylation modification is not limited to NF-κB subunits, but it also encompasses the diverse regulators of NF-κB signaling. The differential site-specific phosphorylation of NF-κB itself or some NF-κB regulators can result in dysregulated NF-κB signaling, often culminating in events that induce cancer progression and other hyper NF-κB related diseases, such as inflammation, cardiovascular diseases, diabetes, as well as neurodegenerative diseases, etc. In this review, we discuss the regulatory role of phosphorylation in NF-κB signaling and the mechanisms through which they aid cancer progression. Additionally, we highlight some of the known and novel NF-κB regulators that are frequently subjected to phosphorylation. Finally, we provide some future perspectives in terms of drug development to target kinases that regulate NF-κB signaling for cancer therapeutic purposes. Full article

(This article belongs to the Special Issue Protein Phosphorylation in Cancer: Unraveling the Signaling Pathways)

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23 pages, 1839 KiB

Open AccessReview

GSK3α: An Important Paralog in Neurodegenerative Disorders and Cancer

by Octavio Silva-García, Ricarda Cortés-Vieyra, Francisco N. Mendoza-Ambrosio, Guillermo Ramírez-Galicia and Víctor M. Baizabal-Aguirre

Biomolecules 2020, 10(12), 1683; https://doi.org/10.3390/biom10121683 - 16 Dec 2020

Cited by 8 | Viewed by 3466

Abstract

The biological activity of the enzyme glycogen synthase kinase-3 (GSK3) is fulfilled by two paralogs named GSK3α and GSK3β, which possess both redundancy and specific functions. The upregulated activity of these proteins is linked to the development of disorders such as neurodegenerative disorders [...] Read more.

The biological activity of the enzyme glycogen synthase kinase-3 (GSK3) is fulfilled by two paralogs named GSK3α and GSK3β, which possess both redundancy and specific functions. The upregulated activity of these proteins is linked to the development of disorders such as neurodegenerative disorders (ND) and cancer. Although various chemical inhibitors of these enzymes restore the brain functions in models of ND such as Alzheimer’s disease (AD), and reduce the proliferation and survival of cancer cells, the particular contribution of each paralog to these effects remains unclear as these molecules downregulate the activity of both paralogs with a similar efficacy. Moreover, given that GSK3 paralogs phosphorylate more than 100 substrates, the simultaneous inhibition of both enzymes has detrimental effects during long-term inhibition. Although the GSK3β kinase function has usually been taken as the global GSK3 activity, in the last few years, a growing interest in the study of GSK3α has emerged because several studies have recognized it as the main GSK3 paralog involved in a variety of diseases. This review summarizes the current biological evidence on the role of GSK3α in AD and various types of cancer. We also provide a discussion on some strategies that may lead to the design of the paralog-specific inhibition of GSK3α. Full article

(This article belongs to the Special Issue Protein Phosphorylation in Cancer: Unraveling the Signaling Pathways)

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21 pages, 2092 KiB

Open AccessReview

Dual Role of the PTPN13 Tyrosine Phosphatase in Cancer

by Soha Mcheik, Leticia Aptecar, Peter Coopman, Véronique D’Hondt and Gilles Freiss

Biomolecules 2020, 10(12), 1659; https://doi.org/10.3390/biom10121659 - 11 Dec 2020

Cited by 15 | Viewed by 3634

Abstract

In this review article, we present the current knowledge on PTPN13, a class I non-receptor protein tyrosine phosphatase identified in 1994. We focus particularly on its role in cancer, where PTPN13 acts as an oncogenic protein and also a tumor suppressor. To try [...] Read more.

In this review article, we present the current knowledge on PTPN13, a class I non-receptor protein tyrosine phosphatase identified in 1994. We focus particularly on its role in cancer, where PTPN13 acts as an oncogenic protein and also a tumor suppressor. To try to understand these apparent contradictory functions, we discuss PTPN13 implication in the FAS and oncogenic tyrosine kinase signaling pathways and in the associated biological activities, as well as its post-transcriptional and epigenetic regulation. Then, we describe PTPN13 clinical significance as a prognostic marker in different cancer types and its impact on anti-cancer treatment sensitivity. Finally, we present future research axes following recent findings on its role in cell junction regulation that implicate PTPN13 in cell death and cell migration, two major hallmarks of tumor formation and progression. Full article

(This article belongs to the Special Issue Protein Phosphorylation in Cancer: Unraveling the Signaling Pathways)

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17 pages, 814 KiB

Open AccessFeature PaperReview

PP2A-B55 Holoenzyme Regulation and Cancer

by Perrine Goguet-Rubio, Priya Amin, Sushil Awal, Suzanne Vigneron, Sophie Charrasse, Francisca Mechali, Jean Claude Labbé, Thierry Lorca and Anna Castro

Biomolecules 2020, 10(11), 1586; https://doi.org/10.3390/biom10111586 - 22 Nov 2020

Cited by 10 | Viewed by 3704

Abstract

Protein phosphorylation is a post-translational modification essential for the control of the activity of most enzymes in the cell. This protein modification results from a fine-tuned balance between kinases and phosphatases. PP2A is one of the major serine/threonine phosphatases that is involved in [...] Read more.

Protein phosphorylation is a post-translational modification essential for the control of the activity of most enzymes in the cell. This protein modification results from a fine-tuned balance between kinases and phosphatases. PP2A is one of the major serine/threonine phosphatases that is involved in the control of a myriad of different signaling cascades. This enzyme, often misregulated in cancer, is considered a tumor suppressor. In this review, we will focus on PP2A-B55, a particular holoenzyme of the family of the PP2A phosphatases whose specific role in cancer development and progression has only recently been highlighted. The discovery of the Greatwall (Gwl)/Arpp19-ENSA cascade, a new pathway specifically controlling PP2A-B55 activity, has been shown to be frequently altered in cancer. Herein, we will review the current knowledge about the mechanisms controlling the formation and the regulation of the activity of this phosphatase and its misregulation in cancer. Full article

(This article belongs to the Special Issue Protein Phosphorylation in Cancer: Unraveling the Signaling Pathways)

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