Calcium in tumour metastasis: new roles for known actors.

In most cases, metastasis, not the primary tumour per se, is the main cause of mortality in cancer patients. In order to effectively escape the tumour, enter the circulation and establish secondary growth in distant organs cancer cells must develop an enhanced propensity to migrate. The ubiquitous second messenger Ca²⁺ is a crucial regulator of cell migration. Recently, a number of known molecular players in cellular Ca²⁺ homeostasis, including calcium release-activated calcium channel protein 1 (ORAI1), stromal interaction molecule 1 (STIM1) and transient receptor potential (TRP) channels, have been implicated in tumour cell migration and the metastatic cell phenotype. We discuss how these developments have increased our understanding of the Ca²⁺ dependence of pro-metastatic behaviours.