The store-operated Ca²⁺ entry-mediated signaling is important for cancer spread

Tumor cell migration and invasion are essential steps in the metastatic cascade that has great impact on patient outcomes. Spatial and temporal organization of Ca²⁺ signaling regulates the multiple aspects of migration machinery, including cytoskeletal reorganization, traction force generation, and focal adhesion dynamics. Stromal interaction molecules (STIM) and Orai proteins, recently identified as critical constituents of store-operated Ca²⁺ entry (SOCE), have been implicated in cancer cell migration and tumor metastasis. The clinical significance of STIM proteins and Orai Ca²⁺ channels in tumor progression and their diagnostic and prognostic potentials have also been demonstrated in different types of cancers. Here we review the recent advances in understanding the important roles and regulatory mechanisms of STIM/Orai-mediated SOCE in cancer spread. The clinical implications and the emergence as a selective target for cancer therapeutics are also discussed. This article is part of a Special Issue entitled: Calcium and Cell Fate. Guest Editors: Jacques Haiech, Claus Heizmann, Joachim Krebs, Thierry Capiod and Olivier Mignen.