title: 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 Ca(2+) entry (SOCE) via the Ca(2+) release activated Ca(2+) (CRAC) channels, which are composed of the plasma membrane based Orai channels and the endoplasmic reticulum stromal interaction molecules (STIMs), is a major Ca(2+) 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 Ca(2+) signals affect malignant transformation, tumour growth and invasion is not fully understood. Here, we review recent studies linking Orai-STIM Ca(2+) 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 Ca(2+) signalling.
authors: Department of Dermatology, Venerology and Allergology, University Hospital of the Saarland, Homburg, Germany.
authors: Hedwig
authors: H
authors: Stanisz
authors: Program of Cellular and Molecular Oncogenesis, Melanoma Research Center, The Wistar Institute, Philadelphia, PA, USA.
authors: Adina
authors: A
authors: Vultur
authors: Program of Cellular and Molecular Oncogenesis, Melanoma Research Center, The Wistar Institute, Philadelphia, PA, USA.
authors: Meenhard
authors: M
authors: Herlyn
authors: Department of Dermatology, University Hospital Essen, Hufelandstraße 55, D-45122, Essen, Germany.
authors: Alexander
authors: A
authors: Roesch
authors: Department of Biophysics, CIPMM, School of Medicine, Saarland University, 66421, Homburg, Germany.
authors: Ivan
authors: 0000-0001-9879-7174
authors: I
authors: Bogeski
mesh_terms: D000818:Animals; D006801:Humans; D008544:Melanocytes / Q000378:metabolism* / Q000473:pathology; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D000071740:ORAI1 Protein / Q000502:physiology*; D000071737:Stromal Interaction Molecule 1 / Q000502:physiology*
chemical_list: D000071740:ORAI1 Protein; D000071737:Stromal Interaction Molecule 1