Insights and perspectives on calcium channel functions in the cockpit of cancerous space invaders.

Development of metastasis causes the most serious clinical consequences of cancer and is responsible for over 90 % of cancer-related deaths. Hence, a better understanding of the mechanisms that drive metastasis formation appears critical for drug development designed to prevent the spread of cancer and related mortality. Metastasis dissemination is a multistep process supported by the increased motility and invasiveness capacities of tumor cells. To succeed in overcoming the mechanical constraints imposed by the basement membrane and surrounding tissues, cancer cells reorganize their focal adhesions or extend acto-adhesive cellular protrusions, called invadosomes, that can both contact the extracellular matrix and tune its degradation through metalloprotease activity. Over the last decade, accumulating evidence has demonstrated that altered Ca channel activities and/or expression promote tumor cell-specific phenotypic changes, such as exacerbated migration and invasion capacities, leading to metastasis formation. While several studies have addressed the molecular basis of Ca channel-dependent cancer cell migration, we are still far from having a comprehensive vision of the Ca channel-regulated mechanisms of migration/invasion. This is especially true regarding the specific context of invadosome-driven invasion. This review aims to provide an overview of the current evidence supporting a central role for Ca channel-dependent signaling in the regulation of these dynamic degradative structures. It will present available data on the few Ca channels that have been studied in that specific context and discuss some potential interesting actors that have not been fully explored yet.