AccScience Publishing / AN / Online First / DOI: 10.36922/an.334
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ORIGINAL RESEARCH ARTICLE

Transient receptor potential melastatin 7 signaling in U251 cell migration and invasion involves calcineurin

Haifan Gong1 ,  Raymond x Wong1 ,  Julia Bandura1 ,  James T. Rutka2 ,  Zhong-Ping Feng1* ,  Hong-Shuo Sun1,2,3,4*
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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
Advanced Neurology 2023, 2(3), 334 https://doi.org/10.36922/an.334
Submitted: 19 January 2023 | Accepted: 10 July 2023 | Published: 24 July 2023
© 2023 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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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 Ca2+-dependent phosphatase, also influences GBM cell survival and migration. However, the role or the relationship between TRPM7 and calcineurin in GBM signaling has not previously been investigated. In this study, we provide evidence that there is a possible interaction between TRPM7 and calcineurin in the GBM cell line U251. Moreover, we employed pharmacological approaches to show that TRPM7 regulates calcineurin function, thereby suggesting that calcineurin is a potential downstream target of TRPM7 signaling in U251 cell migration and invasion.

Keywords
Glioblastoma
Transient receptor potential melastatin 7 channels
Calcineurin
Funding
Canadian Institutes of Health Research
Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grants
Conflict of interest
The authors declare that they have no conflicts of interest with the contents of this article.
References
  1. Nadezhdin KD, Correia L, Narangoda C, et al., 2023, Structural mechanisms of TRPM7 activation and inhibition. Nat Commun, 14: 2639. https://doi.org/10.1038/s41467-023-38362-3

 

  1. Nadler MJ, Hermosura MC, Inabe K, et al., 2001, LTRPC7 is a Mg.ATP-regulated divalent cation channel required for cell viability. Nature, 411: 590–595. https://doi.org/10.1038/35079092

 

  1. Monteilh-Zoller MK, Hermosura MC, Nadler MJS, et al., 2003, TRPM7 provides an ion channel mechanism for cellular entry of trace metal ions. J Gen Physiol, 121: 49–60. https://doi.org/10.1085/jgp.20028740

 

  1. Krapivinsky G, Krapivinsky L, Manasian Y, et al., 2014, The TRPM7 chanzyme is cleaved to release a chromatin-modifying kinase. Cell, 157: 1061–1072. https://doi.org/10.1016/j.cell.2014.03.046

 

  1. Runnels LW, Yue L, Clapham DE, 2001, TRP-PLIK, a bifunctional protein with kinase and ion channel activities. Science, 291: 1043–1047. https://doi.org/10.1126/science.1058519

 

  1. Demeuse P, Penner R, Fleig A, 2006, TRPM7 channel is regulated by magnesium nucleotides via its kinase domain. J Gen Physiol, 127: 421–434. https://doi.org/10.1085/jgp.200509410

 

  1. Ji D, Fleig A, Horgen FD, et al., 2022, Modulators of TRPM7 and its potential as a drug target for brain tumours. Cell Calcium, 101: 102521. https://doi.org/10.1016/j.ceca.2021.102521

 

  1. Cao R, Meng Z, Liu T, et al., 2016, Decreased TRPM7 inhibits activities and induces apoptosis of bladder cancer cells via ERK1/2 pathway. Oncotarget, 7: 72941–72960. https://doi.org/10.18632/oncotarget.12146

 

  1. Huang J, Furuya H, Faouzi M, et al., 2017, Inhibition of TRPM7 suppresses cell proliferation of colon adenocarcinoma in vitro and induces hypomagnesemia in vivo without affecting azoxymethane-induced early colon cancer in mice. Cell Commun Signal, 15: 30. https://doi.org/10.1186/s12964-017-0187-9

 

  1. Middelbeek J, Kuipers AJ, Henneman L, et al., 2012, TRPM7 is required for breast tumor cell metastasis. Cancer Res, 72: 4250–4261. https://doi.org/10.1158/0008-5472.can-11-3863

 

  1. Chen JP, Luan Y, You CX, et al., 2010, TRPM7 regulates the migration of human nasopharyngeal carcinoma cell by mediating Ca(2+) influx. Cell Calcium, 47: 425–432. https://doi.org/10.1016/j.ceca.2010.03.003

 

  1. Ostrom QT, Gittleman H, Fulop J, et al., 2015, CBTRUS statistical Report: Primary brain and central nervous system tumors diagnosed in the United States in 2008-2012. Neuro Oncol, 17: iv1–iv62. https://doi.org/10.1093/neuonc/nov189

 

  1. Stupp R, Mason WP, van den Bent MJ, et al., 2005, Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med, 352: 987–996. https://doi.org/10.1056/nejmoa043330

 

  1. Wu W, Klockow JL, Zhang M, et al., 2021, Glioblastoma multiforme (GBM): An overview of current therapies and mechanisms of resistance. Pharmacol Res, 171: 105780. https://doi.org/10.1016/j.phrs.2021.105780

 

  1. Wong R, Gong H, Alanazi R, et al., 2020, Inhibition of TRPM7 with waixenicin A reduces glioblastoma cellular functions. Cell Calcium, 92: 102307. https://doi.org/10.1016/j.ceca.2020.102307

 

  1. Chen WL, Barszczyk A, Turlova E, et al., 2015, Inhibition of TRPM7 by carvacrol suppresses glioblastoma cell proliferation, migration and invasion. Oncotarget, 6: 16321–16340. https://doi.org/10.18632/oncotarget.3872

 

  1. Chen WL, Turlova E, Sun CLF, et al., 2015, Xyloketal B suppresses glioblastoma cell proliferation and migration in vitro through inhibiting TRPM7-regulated PI3K/Akt and MEK/ERK signaling pathways. Mar Drugs, 13: 2505–2525. https://doi.org/10.3390/md13042505

 

  1. Leng TD, Li MH, Shen JF, et al., 2015, Suppression of TRPM7 inhibits proliferation, migration, and invasion of malignant human glioma cells. CNS Neurosci Ther, 21: 252–261. https://doi.org/10.1111/cns.12354

 

  1. Liu M, Inoue K, Leng T, et al., 2014, TRPM7 channels regulate glioma stem cell through STAT3 and Notch signaling pathways. Cell Signal, 26: 2773–2781. https://doi.org/10.1016/j.cellsig.2014.08.020

 

  1. Wong R, Turlova E, Feng ZP, et al., 2017, Activation of TRPM7 by naltriben enhances migration and invasion of glioblastoma cells. Oncotarget, 8: 11239–11248. https://doi.org/10.18632/oncotarget.14496

 

  1. Tian Y, Yang T, Yu S, et al., 2018, Prostaglandin E2 increases migration and proliferation of human glioblastoma cells by activating transient receptor potential melastatin 7 channels. J Cell Mol Med, 22: 6327–6337. https://doi.org/10.1111/jcmm.13931

 

  1. Turlova E, Wong R, Xu B, et al., 2021, TRPM7 mediates neuronal cell death upstream of calcium/calmodulin-dependent protein kinase II and calcineurin mechanism in neonatal hypoxic-ischemic brain injury. Transl Stroke Res, 12: 164–184. https://doi.org/10.1007/s12975-020-00810-3

 

  1. Brun M, Glubrecht DD, Baksh S, et al., 2013, Calcineurin regulates nuclear factor I dephosphorylation and activity in malignant glioma cell lines. J Biol Chem, 288: 24104–24115. https://doi.org/10.1074/jbc.M113.455832

 

  1. Sliwa M, Markovic D, Gabrusiewicz K, et al., 2007, The invasion promoting effect of microglia on glioblastoma cells is inhibited by cyclosporin A. Brain, 130: 476–489. https://doi.org/10.1093/brain/awl263

 

  1. Kaleka KS, Petersen AN, Florence MA, et al., 2012, Pull-down of calmodulin-binding proteins. J Vis Exp, 59: 3502. https://doi.org/10.3791/3502

 

  1. Han W, Ming M, He TC, et al., 2010, Immunosuppressive cyclosporin A activates AKT in keratinocytes through PTEN suppression: Implications in skin carcinogenesis. J Biol Chem, 285: 11369–11377. https://doi.org/10.1074/jbc.M109.028142

 

  1. Kim TY, Shin SK, Song MY, et al., 2012, Identification of the phosphorylation sites on intact TRPM7 channels from mammalian cells. Biochem Biophys Res Commun, 417: 1030–1034. https://doi.org/10.1016/j.bbrc.2011.12.085

 

  1. Clark K, Middelbeek J, Morrice NA, et al., 2008, Massive autophosphorylation of the Ser/Thr-rich domain controls protein kinase activity of TRPM6 and TRPM7. PLoS One, 3: e1876. https://doi.org/10.1371/journal.pone.0001876

 

  1. Hornbeck PV, Zhang B, Murray B, et al., 2015, PhosphoSitePlus, 2014: Mutations, PTMs and recalibrations. Nucleic Acids Res, 43: D512–D520.

 

  1. Czirják G, Enyedi P, 2006, Targeting of calcineurin to an NFAT-like docking site is required for the calcium-dependent activation of the background K+ channel, TRESK. J Biol Chem, 281: 14677–14682. https://doi.org/10.1074/jbc.M602495200

 

  1. Li H, Rao A, Hogan PG, 2011, Interaction of calcineurin with substrates and targeting proteins. Trends Cell Biol, 21: 91–103. https://doi.org/10.1016/j.tcb.2010.09.011

 

  1. Czirják G, Enyedi P, 2014, The LQLP calcineurin docking site is a major determinant of the calcium-dependent activation of human TRESK background K+ channel. J Biol Chem, 289: 29506–29518. https://doi.org/10.1074/jbc.M114.577684

 

  1. Ryazanova LV, Dorovkov MV, Ansari A, et al., 2004, Characterization of the protein kinase activity of TRPM7/ ChaK1, a protein kinase fused to the transient receptor potential ion channel. J Biol Chem, 279: 3708–3716. https:// doi.org/10.1074/jbc.M308820200

 

  1. Yang X, Li G, Xue Q, et al., 2017, Calcineurin/P-ERK/ Egr-1 pathway is involved in fear memory impairment after isoflurane exposure in mice. Sci Rep, 7: 13947. https://doi.org/10.1038/s41598-017-13975-z

 

  1. Schreck KC, Allen AN, Wang J, et al., 2020, Combination MEK and mTOR inhibitor therapy is active in models of glioblastoma. Neurooncol Adv, 2: vdaa138. https://doi.org/10.1093/noajnl/vdaa138

 

  1. Kim JY, Kim YJ, Lee S, et al., 2009, The critical role of ERK in death resistance and invasiveness of hypoxia-selected glioblastoma cells. BMC Cancer, 9: 27. https://doi.org/10.1186/1471-2407-9-27

 

37. Behrooz AB, Talaie Z, Jusheghani F, et al., 2022, Wnt and PI3K/Akt/mTOR survival pathways as therapeutic targets in glioblastoma. Int J Mol Sci, 23: 1353. https://doi.org/10.3390/ijms23031353

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Advanced Neurology, Electronic ISSN: 2810-9619 Print ISSN: 3060-8589, Published by AccScience Publishing
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