L-type calcium channels regulate filopodia stability and cancer cell invasion downstream of integrin signalling

Guillaume Jacquemet (), Habib Baghirov, Maria Georgiadou, Harri Sihto, Emilia Peuhu, Pierre Cettour-Janet, Tao He, Merja Perälä, Pauliina Kronqvist, Heikki Joensuu and Johanna Ivaska ()
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Guillaume Jacquemet: Turku Centre for Biotechnology, University of Turku
Habib Baghirov: Turku Centre for Biotechnology, University of Turku
Maria Georgiadou: Turku Centre for Biotechnology, University of Turku
Harri Sihto: Laboratory of Molecular Oncology, Translational Cancer Biology program, University of Helsinki
Emilia Peuhu: Turku Centre for Biotechnology, University of Turku
Pierre Cettour-Janet: Turku Centre for Biotechnology, University of Turku
Tao He: VTT Medical Biotechnology, Technical Research Centre of Finland
Merja Perälä: VTT Medical Biotechnology, Technical Research Centre of Finland
Pauliina Kronqvist: University of Turku and Turku University Hospital
Heikki Joensuu: Laboratory of Molecular Oncology, Translational Cancer Biology program, University of Helsinki
Johanna Ivaska: Turku Centre for Biotechnology, University of Turku

Nature Communications, 2016, vol. 7, issue 1, 1-17

Abstract: Abstract Mounting in vitro, in vivo and clinical evidence suggest an important role for filopodia in driving cancer cell invasion. Using a high-throughput microscopic-based drug screen, we identify FDA-approved calcium channel blockers (CCBs) as potent inhibitors of filopodia formation in cancer cells. Unexpectedly, we discover that L-type calcium channels are functional and frequently expressed in cancer cells suggesting a previously unappreciated role for these channels during tumorigenesis. We further demonstrate that, at filopodia, L-type calcium channels are activated by integrin inside-out signalling, integrin activation and Src. Moreover, L-type calcium channels promote filopodia stability and maturation into talin-rich adhesions through the spatially restricted regulation of calcium entry and subsequent activation of the protease calpain-1. Altogether we uncover a novel and clinically relevant signalling pathway that regulates filopodia formation in cancer cells and propose that cycles of filopodia stabilization, followed by maturation into focal adhesions, directs cancer cell migration and invasion.

Date: 2016
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DOI: 10.1038/ncomms13297

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