title: Calcium sensing receptor signalling in physiology and cancer.
abstract: The calcium sensing receptor (CaSR) is a class C G-protein-coupled receptor that is crucial for the feedback regulation of extracellular free ionised calcium homeostasis. While extracellular calcium (Ca(2+)o) is considered the primary physiological ligand, the CaSR is activated physiologically by a plethora of molecules including polyamines and l-amino acids. Activation of the CaSR by different ligands has the ability to stabilise unique conformations of the receptor, which may lead to preferential coupling of different G proteins; a phenomenon termed 'ligand-biased signalling'. While mutations of the CaSR are currently not linked with any malignancies, altered CaSR expression and function are associated with cancer progression. Interestingly, the CaSR appears to act both as a tumour suppressor and an oncogene, depending on the pathophysiology involved. Reduced expression of the CaSR occurs in both parathyroid and colon cancers, leading to loss of the growth suppressing effect of high Ca(2+)o. On the other hand, activation of the CaSR might facilitate metastasis to bone in breast and prostate cancer. A deeper understanding of the mechanisms driving CaSR signalling in different tissues, aided by a systems biology approach, will be instrumental in developing novel drugs that target the CaSR or its ligands in cancer. This article is part of a Special Issue entitled: 12th European Symposium on Calcium.
authors.affiliation: Cardiff School of Biosciences, Cardiff, UK.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Brennan
authors.forename: Ursula
authors.initials: U
authors.lastname: Thiem
authors.forename: Susanne
authors.initials: S
authors.lastname: Roth
authors.forename: Abhishek
authors.initials: A
authors.lastname: Aggarwal
authors.forename: Irfete Sh
authors.initials: ISh
authors.lastname: Fetahu
authors.forename: Samawansha
authors.initials: S
authors.lastname: Tennakoon
authors.forename: Ana Rita
authors.initials: AR
authors.lastname: Gomes
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Brandi
authors.forename: Frank
authors.initials: F
authors.lastname: Bruggeman
authors.forename: Romuald
authors.initials: R
authors.lastname: Mentaverri
authors.forename: Daniela
authors.initials: D
authors.lastname: Riccardi
authors.forename: Enikö
authors.initials: E
authors.lastname: Kallay
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D044169:Receptors, Calcium-Sensing / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D044169:Receptors, Calcium-Sensing; D002118:Calcium