{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T17:53:30Z","timestamp":1781632410469,"version":"3.54.5"},"reference-count":64,"publisher":"American Physiological Society","issue":"6","license":[{"start":{"date-parts":[[2023,9,16]],"date-time":"2023-09-16T00:00:00Z","timestamp":1694822400000},"content-version":"vor","delay-in-days":258,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["TRR-152"],"award-info":[{"award-number":["TRR-152"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,9,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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 \u03b1-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.<\/jats:p>","DOI":"10.1093\/function\/zqad053","type":"journal-article","created":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T23:42:17Z","timestamp":1694821337000},"source":"Crossref","is-referenced-by-count":11,"title":["Inactivation of TRPM7 Kinase Targets AKT Signaling and Cyclooxygenase-2 Expression in Human CML Cells"],"prefix":"10.1152","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7491-9405","authenticated-orcid":false,"given":"Birgit","family":"Hoeger","sequence":"first","affiliation":[{"name":"Institute of Pharmacology, Johannes Kepler University Linz , Altenbergerstr. 69, 4040 Linz and Krankenhausstr. 5, 4020 Linz , Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiebke","family":"Nadolni","sequence":"additional","affiliation":[{"name":"Walther Straub 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