title: Reciprocal regulation of actin cytoskeleton remodelling and cell migration by Ca2+ and Zn2+: role of TRPM2 channels.
abstract: Cell migration is a fundamental feature of tumour metastasis and angiogenesis. It is regulated by a variety of signalling molecules including H2O2 and Ca(2+) Here, we asked whether the H2O2-sensitive transient receptor potential melastatin 2 (TRPM2) Ca(2+) channel serves as a molecular link between H2O2 and Ca(2+) H2O2-mediated activation of TRPM2 channels induced filopodia formation, loss of actin stress fibres and disassembly of focal adhesions, leading to increased migration of HeLa and prostate cancer (PC)-3 cells. Activation of TRPM2 channels, however, caused intracellular release of not only Ca(2+) but also of Zn(2+) Intriguingly, elevation of intracellular Zn(2+) faithfully reproduced all of the effects of H2O2, whereas Ca(2+) showed opposite effects. Interestingly, H2O2 caused increased trafficking of Zn(2+)-enriched lysosomes to the leading edge of migrating cells, presumably to impart polarisation of Zn(2+) location. Thus, our results indicate that a reciprocal interplay between Ca(2+) and Zn(2+) regulates actin remodelling and cell migration; they call for a revision of the current notion that implicates an exclusive role for Ca(2+) in cell migration.
authors.affiliation: School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK Multidisciplinary Cardiovascular Research Centre, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Li
authors.affiliation: School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK Multidisciplinary Cardiovascular Research Centre, University of Leeds, Leeds LS2 9JT, UK.
authors.forename: Nada
authors.initials: N
authors.lastname: Abuarab
authors.affiliation: School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK Multidisciplinary Cardiovascular Research Centre, University of Leeds, Leeds LS2 9JT, UK a.sivaprasadarao@leeds.ac.uk.
authors.forename: Asipu
authors.identifier: 0000-0002-6755-3502
authors.initials: A
authors.lastname: Sivaprasadarao
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000235:genetics; D016923:Cell Death / Q000235:genetics; D002465:Cell Movement / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008247:Lysosomes / Q000235:genetics / Q000378:metabolism; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000378:metabolism; D011554:Pseudopodia / Q000235:genetics; D050053:TRPM Cation Channels / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics; D015032:Zinc / Q000378:metabolism
chemical_list: D050053:TRPM Cation Channels; C121934:TRPM2 protein, human; D006861:Hydrogen Peroxide; D015032:Zinc; D002118:Calcium
keywords: Actin cytoskeleton dynamics; Ca2+; Cell migration; Focal adhesion; Lysosomal trafficking; TRPM2 channel; Zn2+