Cell migration is a fundamental feature of tumour metastasis and angiogenesis. It is regulated by a variety of signalling molecules including H2O2and Ca(2+) Here, we asked if the H2O2-sensitive Transient Receptor Potential Melastatin 2 (TRPM2) calcium channel serves as a molecular link between H2O2and Ca(2+) H2O2activation of TRPM2 channels induced filopodia formation, loss of actin stress fibres and disassembly of focal adhesions, leading to increased migration of HeLa and PC (prostate cancer)-3 cells. Activation of TRPM2 channels, however, caused intracellular release of not only Ca(2+), but also Zn(2+) Intriguingly, elevation of intracellular Zn(2+)faithfully reproduced all of the effects of H2O2, while Ca(2+)showed opposite effects. Interestingly, H2O2caused increased trafficking of Zn(2+)-enriched lysosomes to the leading edge of migrating cells, presumably to impart polarisation of Zn(2+) 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.
Journal of cell science. 2016 Apr 11 [Epub ahead of print]
Fangfang Li, Nada Abuarab, Asipu Sivaprasadarao
School of Biomedical Sciences, University of Leeds, LS2 9JT, Leeds, UK., Faculty of Biological Sciences, University of Leeds, LS2 9JT, Leeds, UK., Multidisciplinary Cardiovascular Research Centre, University of Leeds, LS2 9JT, Leeds, UK .