Low molecular weight protein tyrosine phosphatase as signaling hub of cancer hallmarks
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Cellular and Molecular Life Sciences
REVIEW
Low molecular weight protein tyrosine phosphatase as signaling hub of cancer hallmarks Alessandra V. S. Faria1,2 · Emanuella Maria Barreto Fonseca1,3 · Helon Guimarães Cordeiro1 · Stefano Piatto Clerici1 · Carmen Veríssima Ferreira‑Halder1 Received: 11 June 2020 / Revised: 21 August 2020 / Accepted: 22 September 2020 © Springer Nature Switzerland AG 2020
Abstract In the past decade, significant progress has been made in understanding the role of protein tyrosine phosphatase as a positive regulator of tumor progression. In this scenario, our group was one of the first to report the involvement of the low molecular weight protein tyrosine phosphatase (LMWPTP or ACP1) in the process of resistance and migration of tumor cells. Later, we and others demonstrated a positive correlation between the amount of this enzyme in human tumors and the poor prognosis. With this information in mind, we asked if LMWPTP contribution to metastasis, would it have an action beyond the primary tumor site. We know that the amount of this enzyme in the tumor cell correlates positively with the ability of cancer cells to interact with platelets, an indication that this enzyme is also important for the survival of these cells in the bloodstream. Here, we discuss several molecular aspects that support the idea of LMWPTP as a signaling hub of cancer hallmarks. Chemical and genetic modulation of LMWPTP proved to shut down signaling pathways associated with cancer aggressiveness. Therefore, advances in the development of LMWPTP inhibitors have great applicability in human diseases such as cancer. Keywords Low molecular weight protein tyrosine phosphatase · Signaling hub · Cancer hallmarks · Metabolism reprogramming
Introduction Eukaryotic cells respond to various stimuli in the microenvironment by modulating signal transduction pathways, which is dependent on post-translational protein modification. Among the different post-translation modifications, phosphorylation/dephosphorylation is the main form of rapid and reversible covalent modulation of proteins [1, 2]. Phosphorylation of a protein can create a new recognition site for protein–protein interactions, control protein stability, and, more importantly, can regulate enzyme/protein activity and localization. Thus, the phosphorylation of tyrosine, serine, and threonine residues, mediated by the balance between * Carmen Veríssima Ferreira‑Halder [email protected] 1
Department of Biochemistry and Tissue Biology, University of Campinas, Campinas, São Paulo, Brazil
2
Department of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
3
Federal Institute of São Paulo, São Roque, São Paulo, Brazil
the action of protein kinases (PKs) and protein phosphatases (PPs) is recognized as a crucial factor in the generation and regulation of signals necessary for survival, proliferation, cell differentiation, and death [2]. In this context, abnormal changes in the activity of these enzymes can pr
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