Metastatic disease represents the major cause of death in oncologic patients worldwide. Accumulating evidence have highlighted the relevance of a small population of cancer cells, named cancer stem cells (CSCs), in the resistance to therapies, as well as cancer recurrence and metastasis. Standard anti-cancer treatments are not always conclusively curative, posing an urgent need to discover new targets for an effective therapy. Kinases and phosphatases are implicated in many cellular processes, such as proliferation, differentiation and oncogenic transformation. These proteins are crucial regulators of intracellular signaling pathways mediating multiple cellular activities. Therefore, alterations in kinases and phosphatases functionality is a hallmark of cancer. Notwithstanding the role of kinases and phosphatases in cancer has been widely investigated, their aberrant activation in the compartment of CSCs is nowadays being explored as new potential Achille's heel to strike. Here, we provide a comprehensive overview of the major protein kinases and phosphatases pathways by which CSCs can evade normal physiological constraints on survival, growth, and invasion. Moreover, we discuss the potential of inhibitors of these proteins in counteracting CSCs expansion during cancer development and progression.
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http://dx.doi.org/10.3389/fcell.2021.690306 | DOI Listing |
Am J Cancer Res
December 2024
Department of Pharmacology and Toxicology, Medical College of Wisconsin Milwaukee, Wisconsin 53226, USA.
Cancer cell overexpresses numerus proteins, however, how these up-regulated proteins, especially those enzymatically opposite kinases and phosphatases, act together to promote oncogenesis is unknown. Here, we reported that protein tyrosine phosphatase H1 (PTPH1) is a scaffold protein for receptor tyrosine kinase (HER2) to potentiate breast tumorigenesis. PTPH1 utilizes its PDZ domain to bind HER2, p38γ, PBK, and YAP1 and to increase HER2 nuclear translocation, stemness, and oncogenesis.
View Article and Find Full Text PDFCurr Biol
January 2025
Department of Cell Biology, Duke University Medical Center, Durham, NC 27705, USA; Duke Center for Quantitative Living Systems, Duke University Medical Center, Durham, NC 27710, USA. Electronic address:
Anaphase is tightly controlled spatiotemporally to ensure proper separation of chromosomes. The mitotic spindle, the self-organized microtubule structure driving chromosome segregation, scales in size with the available cytoplasm. Yet, the relationship between spindle size and chromosome movement remains poorly understood.
View Article and Find Full Text PDFJ Chem Phys
January 2025
Institute of Physics, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
One of the hypothesized functions of biomolecular condensates is to act as chemical reactors, where chemical reactions can be modulated, i.e., accelerated or slowed down, while substrate molecules enter and products exit from the condensate.
View Article and Find Full Text PDFBrief Bioinform
November 2024
Department of Bioinformatics and Systems Biology, MOE Key Laboratory of Molecular Biophysics, Hubei Bioinformatics and Molecular Imaging Key Laboratory, Center for Artificial Intelligence Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Luoyu Road 1037, Wuhan, Hubei 430074, China.
Protein phosphorylation is dynamically and reversibly regulated by protein kinases and protein phosphatases, and plays an essential role in orchestrating a wide range of biological processes. Although a number of tools have been developed for predicting kinase-specific phosphorylation sites (p-sites), computational prediction of phosphatase-specific dephosphorylation sites remains to be a great challenge. In this study, we manually curated 4393 experimentally identified site-specific phosphatase-substrate relationships for 3463 dephosphorylation sites occurring on phosphoserine, phosphothreonine, and/or phosphotyrosine residues, from the literature and public databases.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Biochemistry, Brandeis University, Waltham, MA 02454.
Reversible protein phosphorylation directs essential cellular processes including cell division, cell growth, cell death, inflammation, and differentiation. Because protein phosphorylation drives diverse diseases, kinases and phosphatases have been targets for drug discovery, with some achieving remarkable clinical success. Most protein kinases are activated by phosphorylation of their activation loops, which shifts the conformational equilibrium of the kinase toward the active state.
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