Ca²⁺ Signaling in Cytoskeletal Reorganization, Cell Migration, and Cancer Metastasis

Figure 1

Local Ca²⁺ pulses control retraction and adhesion around the leading edge of migrating cells. (a) Polarized receptor tyrosine kinase (RTK) signaling generates inositol triphosphate (IP₃) in front of migrating cells, which sensitizes IP₃ receptors (IP₃R) to release Ca²⁺ periodically from the endoplasmic reticulum (ER). IP₃R are also triggered by Ca²⁺-induced Ca²⁺ release (CICR), which originates from transient receptor potential (TRP) channels, mainly TRPM7. (b) Local Ca²⁺ pulses activate myosin light chain kinase (MLCK, shown as ML in the illustration), which phosphorylates myosin II for proper actin treadmilling and recycling. (c) Local Ca²⁺ pulse-triggered myosin contraction also enhances the formation of focal adhesion (FA) complexes, probably via force-induced positive feedback. Please notice the temporal correlation (as shown by dotted lines and arrowheads) and oscillatory dynamics between local Ca²⁺ pulses, front retraction, and FA. MY: myosin II; ML: myosin light chain kinase; I: integrin; ECM: extracellular matrix.