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

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, tumour 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.