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http://purl.uniprot.org/citations/37786778http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/37786778http://www.w3.org/2000/01/rdf-schema#comment"Cyclooxygenase-2 (COX-2) is a key regulator of inflammation. High constitutive COX-2 expression enhances survival and proliferation of cancer cells, and adversely impacts antitumor immunity. The expression of COX-2 is modulated by various signaling pathways. Recently, we identified the melastatin-like transient-receptor-potential-7 (TRPM7) channel-kinase as modulator of immune homeostasis. TRPM7 protein is essential for leukocyte proliferation and differentiation, and upregulated in several cancers. It comprises of a cation channel and an atypical α-kinase, linked to inflammatory cell signals and associated with hallmarks of tumor progression. A role in leukemia has not been established, and signaling pathways are yet to be deciphered. We show that inhibiting TRPM7 channel-kinase in chronic myeloid leukemia (CML) cells results in reduced constitutive COX-2 expression. By utilizing a CML-derived cell line, HAP1, harboring CRISPR/Cas9-mediated TRPM7 knockout, or a point mutation inactivating TRPM7 kinase, we could link this to reduced activation of AKT serine/threonine kinase and mothers against decapentaplegic homolog 2 (SMAD2). We identified AKT as a direct in vitro substrate of TRPM7 kinase. Pharmacologic blockade of TRPM7 in wildtype HAP1 cells confirmed the effect on COX-2 via altered AKT signaling. Addition of an AKT activator on TRPM7 kinase-dead cells reconstituted the wildtype phenotype. Inhibition of TRPM7 resulted in reduced phosphorylation of AKT and diminished COX-2 expression in peripheral blood mononuclear cells derived from CML patients, and reduced proliferation in patient-derived CD34+ cells. These results highlight a role of TRPM7 kinase in AKT-driven COX-2 expression and suggest a beneficial potential of TRPM7 blockade in COX-2-related inflammation and malignancy."xsd:string
http://purl.uniprot.org/citations/37786778http://purl.org/dc/terms/identifier"doi:10.1093/function/zqad053"xsd:string
http://purl.uniprot.org/citations/37786778http://purl.uniprot.org/core/author"Gudermann T."xsd:string
http://purl.uniprot.org/citations/37786778http://purl.uniprot.org/core/author"Breit A."xsd:string
http://purl.uniprot.org/citations/37786778http://purl.uniprot.org/core/author"Hoeger B."xsd:string
http://purl.uniprot.org/citations/37786778http://purl.uniprot.org/core/author"Boekhoff I."xsd:string
http://purl.uniprot.org/citations/37786778http://purl.uniprot.org/core/author"Geisberger R."xsd:string
http://purl.uniprot.org/citations/37786778http://purl.uniprot.org/core/author"Addington L."xsd:string
http://purl.uniprot.org/citations/37786778http://purl.uniprot.org/core/author"Zierler S."xsd:string
http://purl.uniprot.org/citations/37786778http://purl.uniprot.org/core/author"Chubanov V."xsd:string
http://purl.uniprot.org/citations/37786778http://purl.uniprot.org/core/author"Greil R."xsd:string
http://purl.uniprot.org/citations/37786778http://purl.uniprot.org/core/author"Steinritz D."xsd:string
http://purl.uniprot.org/citations/37786778http://purl.uniprot.org/core/author"Zaborsky N."xsd:string
http://purl.uniprot.org/citations/37786778http://purl.uniprot.org/core/author"Hoelting K."xsd:string
http://purl.uniprot.org/citations/37786778http://purl.uniprot.org/core/author"Hampe S."xsd:string
http://purl.uniprot.org/citations/37786778http://purl.uniprot.org/core/author"Nadolni W."xsd:string
http://purl.uniprot.org/citations/37786778http://purl.uniprot.org/core/author"Fraticelli M."xsd:string
http://purl.uniprot.org/citations/37786778http://purl.uniprot.org/core/author"Fraticelli L."xsd:string
http://purl.uniprot.org/citations/37786778http://purl.uniprot.org/core/author"Madlmayr A."xsd:string
http://purl.uniprot.org/citations/37786778http://purl.uniprot.org/core/author"Sperrer V."xsd:string
http://purl.uniprot.org/citations/37786778http://purl.uniprot.org/core/date"2023"xsd:gYear
http://purl.uniprot.org/citations/37786778http://purl.uniprot.org/core/name"Function (Oxf)"xsd:string
http://purl.uniprot.org/citations/37786778http://purl.uniprot.org/core/pages"zqad053"xsd:string
http://purl.uniprot.org/citations/37786778http://purl.uniprot.org/core/title"Inactivation of TRPM7 Kinase Targets AKT Signaling and Cyclooxygenase-2 Expression in Human CML Cells."xsd:string
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