Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.08.13.249169v1?rss=1 Authors: Iamshanova, O., Gordienko, D., Folcher, A., Bokhobza, A., Shapovalov, G., Mariot, P., Allart, L., Desruelles, E., Spriet, C., Diez, R., Oullier, T., Marionneau-Lambot, S., Brisson, L., Geraci, S., Impheng, H., Lehenkyi, V., Haustrate, A., Mihalache, A., Gosset, P., Chadet, S., Lerondel, S., Retif, S., Le Mee, M., Sobilo, J., Roger, S., Fromont, G., Djamgoz, M., Clezardin, P., Monteil, A., Prevarskaya, N. Abstract: Cytosolic Ca2+ oscillations provide signaling input to several effector systems of the cell. These include neuronal development, migration and networking. Although similar signaling events are hijacked by highly aggressive cancer cells, the mechanism(s) driving the 'neuron-like' remodeling of the intracellular ionic signature upon cancer progression remains largely elusive. Here, we identify the 'neuronal' Na+ leak channel, NALCN, in metastatic cells at the hot spots of invadopodia formation and Ca2+ event initiation. Mechanistically, NALCN-mediated Na+ influx associates functionally with plasmalemmal and mitochondrial Na+/Ca2+ exchangers (NCX and NCLX), reactive oxygen species (ROS) and store-operated Ca2+ entry (SOCE)/endoplasmic reticulum Ca2+ uptake (SERCA) systems to generate intracellular Ca2+ oscillations. In turn, the oscillatory activity promotes Src-regulated actin remodeling, Ca2+-dependent secretion of proteolytic enzymes and leads to invadopodogenesis, resulting in tumor progression and metastatic lesions in vivo . Thus, we have uncovered malignant assignment of NALCN giving rise to a critical intracellular Na+/Ca2+ signaling axis. Copy rights belong to original authors. Visit the link for more info