Song, Chiman Bae, Yeonju Jun, JinJoo Lee, Hyomin Kim, Nam Doo Lee, Kyung-Bok Hur, Wooyoung Park, Jae-Yong Sim, Taebo 2024-01-20T02:00:16Z 2024-01-20T02:00:16Z 2021-09-01 2017-04 0304-4165 https://pubs.kist.re.kr/handle/201004/122881 Background: Transient receptor potential melastatin 7 (TRPM7) regulates breast cancer cell proliferation, migration, invasion and metastasis in its ion channel-and kinase domain-dependent manner. The pharmacological effects of TRPM7 ion channel inhibitors on breast cancer cells have been studied, but little is known about the effects of TRPM7 kinase domain inhibitors due to lack of potent TRPM7 kinase inhibitors. Methods: Screening was performed by using TRPM7 kinase assay. Effects of TG100-115 on breast cancer cell proliferation, migration, invasion, myosin IIA phosphorylation, and TRPM7 ion channel activity were assessed by using MTT, wound healing, transwell assay, Western blotting, and patch clamping, respectively. Results: We found that CREB peptide is a potent substrate for the TR-FRET based TRPM7 kinase assay. Using this method, we discovered a new and potent TRPM7 kinase inhibitor, TG100-115. TG100-115 inhibited TRPM7 kinase activity in an ATP competitive fashion with over 70-fold stronger activity than that of rottlerin, known as a TRPM7 kinase inhibitor. TG100-115 has little effect on proliferation of MDA-MB-231 cells, but significantly decreases cell migration and invasion. Moreover, TG100-115 inhibits TRPM7 kinase regulated phosphorylation of the myosin IIA heavy chain and phosphorylation of focal adhesion kinase. TG100-115 also suppressed TRPM7 ion channel activity. Conclusions: TG100-115 can be used as a potent TRPM7 kinase inhibitor and a potent inhibitor of breast cancer cell migration. General significance: TG100-115 could be a useful tool for studying the pharmacological effects of TRPM7 kinase activity aimed at providing insight into new therapeutic approaches to the treatment of breast cancer. (C) 2017 Elsevier B.V. All rights reserved. English Elsevier BV Identification of TG100-115 as a new and potent TRPM7 kinase inhibitor, which suppresses breast cancer cell migration and invasion Article 10.1016/j.bbagen.2017.01.034 1 Biochimica et Biophysica Acta - General Subjects, v.1861, no.4, pp.947 - 957 Biochimica et Biophysica Acta - General Subjects 1861 4 947 957 N scie scopus 000397366200022 2-s2.0-85011964500 Biochemistry & Molecular Biology Biophysics Biochemistry & Molecular Biology Biophysics Article MELASTATIN 7 MG2+ HOMEOSTASIS CHANNEL FUNCTION PROTEIN PROLIFERATION ROTTLERIN ADHESION INACTIVATION WAIXENICIN MECHANISM TRPM7 kinase inhibitor TG100-115 MDA-MB-231 Breast cancer Cell migration Cell invasion