Ca2+ signaling in cytoskeletal reorganization, cell migration, and cancer metastasis

Abstract

Proper control of Ca2+ signaling is mandatory for effective cell migration, which is critical for embryonic development, wound healing, and cancer metastasis. However, how Ca2+ coordinates structural components and signaling molecules for proper cell motility had remained elusive. With the advance of fluorescent live-cell Ca2+ imaging in recent years, we gradually understand how Ca2+ is regulated spatially and temporally in migrating cells, driving polarization, protrusion, retraction, and adhesion at the right place and right time. Here we give an overview about how cells create local Ca2+ pulses near the leading edge, maintain cytosolic Ca2+ gradient from back to front, and restore Ca2+ depletion for persistent cell motility. Differential roles of Ca2+ in regulating various effectors and the interaction of roles of Ca2+ signaling with other pathways during migration are also discussed. Such information might suggest a new direction to control cancer metastasis by manipulating Ca2+ and its associating signaling molecules in a judicious manner.