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

Guillaume Jacquemet (Corresponding Author), Habib Baghirov, Maria Georgiadou, Harri Sihto, Emilia Peuhu, Pierre Cettour-Janet, Tao He, Merja Perälä, Pauliina Kronqvist, Heikki Joensuu, Johanna Ivaska (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

46 Citations (Scopus)

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.
Original languageEnglish
Article number13297
JournalNature Communications
Volume7
DOIs
Publication statusPublished - 2016
MoE publication typeA1 Journal article-refereed

Keywords

  • breast cancer
  • cell invasion
  • integrins

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    Jacquemet, G., Baghirov, H., Georgiadou, M., Sihto, H., Peuhu, E., Cettour-Janet, P., He, T., Perälä, M., Kronqvist, P., Joensuu, H., & Ivaska, J. (2016). L-type calcium channels regulate filopodia stability and cancer cell invasion downstream of integrin signalling. Nature Communications, 7, [13297]. https://doi.org/10.1038/ncomms13297