Page 46 - AN-2-3
P. 46

Advanced Neurology





                                        ORIGINAL RESEARCH ARTICLE
                                        Transient receptor potential melastatin 7

                                        signaling in U251 cell migration and invasion
                                        involves calcineurin



                                                   1
                                                                                               2
                                        Haifan Gong , Raymond Wong , Julia Bandura , James T. Rutka ,
                                                                                1
                                                                  1
                                        Zhong-Ping Feng *, and Hong-Shuo Sun 1,2,3,4*
                                                       1
                                        1 Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario,
                                        Canada
                                        2 Department of Surgery, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
                                        3 Department of Pharmacology and Toxicology, Temerty Faculty of Medicine, University of Toronto,
                                        Toronto, Ontario, Canada
                                        4 Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada



                                        Abstract

                                        Transient receptor potential melastatin 7 (TRPM7) is a divalent cation channel that
                                        has crucial functions in glioblastoma (GBM), which remains the most prevalent and
                                        lethal primary brain tumor in adults. Altering TRPM7 activity has previously been
                                        reported to affect GBM cell function (i.e., migration, invasion, and proliferation),
                                        thus elucidating the TRPM7-mediated signaling pathway in GBM could reveal novel
                                        therapeutic targets. Calcineurin, a Ca -dependent phosphatase, also influences GBM
                                                                      2+
            *Corresponding authors:     cell survival and migration. However, the role or the relationship between TRPM7 and
            Zhong-Ping Feng             calcineurin in GBM signaling has not previously been investigated. In this study, we
            (zp.feng@utoronto.ca)
            Hong-Shuo Sun               provide evidence that there is a possible interaction between TRPM7 and calcineurin
            (hss.sun@utoronto.ca)       in the GBM cell line U251. Moreover, we employed pharmacological approaches to
            Citation: Gong H, Wong R,   show that TRPM7 regulates calcineurin function, thereby suggesting that calcineurin
            Bandura J, et al., 2023, Transient   is a potential downstream target of TRPM7 signaling in U251 cell migration and
            receptor potential melastatin 7   invasion.
            signaling in U251 cell migration and
            invasion involves calcineurin.
             Adv Neuro, 2(3): 334.
            https://doi.org/10.36922/an.334   Keywords: Glioblastoma; Transient receptor potential melastatin 7 channels; Calcineurin
            Received: January 19, 2023
            Accepted: July 10, 2023
            Published Online: July 24, 2023  1. Introduction
            Copyright: © 2023 Author(s).   The ubiquitously expressed transient receptor potential melastatin 7 (TRPM7) channel
            This is an Open-Access article   is  involved in  the  cellular homeostasis of  divalent ions [1-3] .  Containing both an  ion
            distributed under the terms of the   channel and a kinase domain [4-6] , TRPM7 plays a critical role in cancer cell function, and
            Creative Commons Attribution
            License, permitting distribution,   inhibition of overexpressed TRPM7 has been identified as a potential pharmaceutical
            and reproduction in any medium,   intervention [7-11] .
            provided the original work is
            properly cited.               Glioblastoma (GBM) is the most lethal malignant primary brain tumor in adults, with
            Publisher’s Note: AccScience   an estimated 5-year survival rate of 5.1% [12,13] . Current treatment approaches, including
            Publishing remains neutral with   surgical resection, radiotherapy, and chemotherapy, are untargeted, resulting in suboptimal
            regard to jurisdictional claims in   [14]
            published maps and institutional   outcomes . Thus, novel treatment options are urgently required. Over the past decade,
            affiliations.               there has been growing evidence demonstrating the critical role of TRPM7 in regulating


            Volume 2 Issue 3 (2023)                         1                          https://doi.org/10.36922/an.334
   41   42   43   44   45   46   47   48   49   50   51