Biophysics of Cancer: Cellular Excitability (“CELEX”) Hypothesis of Metastasis

Biophysics of Cancer: Cellular Excitability (“CELEX”) Hypothesis of Metastasis

This article advances a novel hypothesis of metastasis called “CELEX” (for cellular excitability) and presents the current evidence for it. The CELEX hypothesis is based upon concerted expression of voltage-gated ion, particularly Na+ and K+, channels during cancer progression. Electrophysiological recordings from human carcinoma cell lines have shown that, unlike weakly/nonmetastatic cells, cells that have strong metastatic potential express voltage-gated Na+ channels and much reduced outward, mainly K+ currents. Furthermore, the Na+ channel expression is selfsustaining by activity-dependent positive feedback. Thus, strongly metastatic carcinoma cells are excitable and, indeed, generate all-or-none type action potentials, despite their epithelial origin.