title: CRAC channels, calcium, and cancer in light of the driver and passenger concept.
abstract: Advances in next-generation sequencing allow very comprehensive analyses of large numbers of cancer genomes leading to an increasingly better characterization and classification of cancers. Comparing genomic data predicts candidate genes driving development, growth, or metastasis of cancer. Cancer driver genes are defined as genes whose mutations are causally implicated in oncogenesis whereas passenger mutations are defined as not being oncogenic. Currently, a list of several hundred cancer driver mutations is discussed including prominent members like TP53, BRAF, NRAS, or NF1. According to the vast literature on Ca(2+) and cancer, Ca(2+) signals and the underlying Ca(2+) channels and transporters certainly influence the development, growth, and metastasis of many cancers. In this review, I focus on the calcium release-activated calcium (CRAC) channel genes STIM and Orai and their role for cancer development, growth, and metastasis. STIM and Orai genes are being discussed in the context of current cancer concepts with a focus on the driver-passenger hypothesis. One result of this discussion is the hypothesis that a driver analysis of Ca(2+) homeostasis-related genes should not be carried out by looking at isolated genes. Rather a pool of “Ca(2+) genes” might be considered to act as one potential cancer driver. 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.
authors.affiliation: Department of Biophysics, Center for Integrative Physiology and Molecular Medicine, Medical Faculty, Building 48, Saarland University, D-66421 Homburg, Germany. Electronic address: markus.hoth@uks.eu.
authors.forename: Markus
authors.initials: M
authors.lastname: Hoth
mesh_terms: D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D000071740:ORAI1 Protein; D000071741:ORAI2 Protein; D000071737:Stromal Interaction Molecule 1; D000071738:Stromal Interaction Molecule 2
chemical_list: D015220:Calcium Channels; D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; D000071741:ORAI2 Protein; C514506:ORAI2 protein, human; C522867:Orai3 protein, human; C103530:STIM1 protein, human; C513279:STIM2 protein, human; D000071737:Stromal Interaction Molecule 1; D000071738:Stromal Interaction Molecule 2; D002118:Calcium
keywords: CRAC channels; CTLA4; Calcium; Cancer; Cancer driver gene; Cancer passenger gene; Checkpoint therapy; Cytotoxic T lymphocytes (CTL); Natural killer (NK) cells; Orai; Orai1; Orai2; Orai3; STIM; STIM1; STIM2; TRPV5; TRPV6; Tumor; Tumor microenvironment