The role of Orai/STIM calcium channels in melanocytes and melanoma

Abstract

Calcium signalling within normal and cancer cells regulates many important cellular functions such as migration, proliferation, differentiation and cytokine secretion.  Store operated Ca²⁺ entry (SOCE) via the Ca²⁺ release activated Ca²⁺ (CRAC) channels, which are composed of the plasma membrane based Orai channels and the endoplasmic reticulum stromal interaction molecules (STIMs), is a major Ca²⁺- entry route in many cell types. Orai and STIM have been implicated in the growth and metastasis of multiple cancers; however, while their involvement in cancer is presently indisputable, how Orai/STIM-controlled Ca²⁺ signals affect malignant transformation, tumor growth, and invasion is not fully understood. Here, we review recent studies linking Orai/STIM Ca²⁺ channels with cancer, with a particular focus on melanoma. We highlight and examine key molecular players and the signalling pathways regulated by Orai and STIM in normal and malignant cells, we expose discrepancies, and we reflect on the potential of Orai/STIMs as anticancer drug targets. Finally, we discuss the functional implications of future discoveries in the field of Ca²⁺ signalling.

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