“…Since Trio was shown to be implicated in controlled turnover of invadopodia during cancer cell invasion, it raised the possibility of NALCN involvement in tumorigenesis (Kwiatkowska et al, 2012;Moshfegh et al, 2014). Furthermore, the elevated tissue Na + concentration has been found to be a highly specific in vivo indicator of malignancy, which can be, at least in part, provided by sustained NALCN-mediated Na + influx (Barrett et al, 2018;Bartha et al, 2008;Haneder et al, 2015;Henzler et al, 2012;Huang et al, 2018;Jacobs et al, 2011;Laymon et al, 2012;Leslie et al, 2019;Ouwerkerk et al, 2003Ouwerkerk et al, , 2007Zaric et al, 2016). Given the tight coupling between Na + and Ca 2+ signaling (Verkhratsky et al, 2018), we hypothesized that in metastatic cancer cells NALCN could provide signaling input encouraging the cell invasion via intracellular Ca 2+ events.…”