Ca²⁺ Signaling and Src Functions in Tumor Cells

Signaling by calcium ion (Ca²⁺) plays a prominent role in cell physiology, and these mechanisms are frequently altered in tumor cells. In this review, we consider the interplay of Ca²⁺ signaling and the functions of the proto-oncogene non-receptor tyrosine kinase c-Src in tumor cells, and the viral oncogenic variant v-Src in transformed cells. Also, other members of the Src-family kinases are considered in this context. The role of Ca²⁺ in the cell is frequently mediated by Ca²⁺-binding proteins, where the Ca²⁺-sensor protein calmodulin (CaM) plays a prominent, essential role in many cellular signaling pathways. Thus, we cover the available information on the role and direct interaction of CaM with c-Src and v-Src in cancerous cells, the phosphorylation of CaM by v-Src/c-Src, and the actions of different CaM-regulated Ser/Thr-protein kinases and the CaM-dependent phosphatase calcineurin on v-Src/c-Src. Finally, we mention some clinical implications of these systems to identify mechanisms that could be targeted for the therapeutic treatment of human cancers.