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

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http://hdl.handle.net/10138/172691

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Jacquemet , G , Baghirov , H , Georgiadou , M , Sihto , H , Peuhu , E , Cettour-Janet , P , He , T , Perala , 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 , vol. 7 , 13297 . https://doi.org/10.1038/ncomms13297

Title: L-type calcium channels regulate filopodia stability and cancer cell invasion downstream of integrin signalling
Author: Jacquemet, Guillaume; Baghirov, Habib; Georgiadou, Maria; Sihto, Harri; Peuhu, Emilia; Cettour-Janet, Pierre; He, Tao; Perala, Merja; Kronqvist, Pauliina; Joensuu, Heikki; Ivaska, Johanna
Contributor: University of Helsinki, Clinicum
University of Helsinki, Clinicum
Date: 2016-12-02
Language: eng
Number of pages: 17
Belongs to series: Nature Communications
ISSN: 2041-1723
URI: http://hdl.handle.net/10138/172691
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.
Subject: BREAST-CANCER
MYOSIN-X
ALPHA(5)BETA(1) INTEGRIN
ESTROGEN-RECEPTOR
MIGRATION
ACTIVATION
ADHESION
METASTASIS
COMPLEX
PROGRESSION
3111 Biomedicine
3122 Cancers
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