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Calcium sensing receptor signalling in physiology and cancer

Brennan, Sarah C., Thiem, Ursula, Roth, Susanne, Aggarwal, Abhishek, Fetahu, Irfete Sh., Tennakoon, Samawansha, Gomes, Ana Rita, Brandi, Maria Luisa, Bruggeman, Frank, Mentaverri, Romuald, Riccardi, Daniela and Kallay, Enikö 2013. Calcium sensing receptor signalling in physiology and cancer. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1833 (7) , pp. 1732-1744. 10.1016/j.bbamcr.2012.12.011

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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 (Ca2 +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 Ca2 +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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Publisher: Elsevier
ISSN: 0167-4889
Funders: Marie Curie ITN
Last Modified: 04 Jun 2017 05:14
URI: http://orca-mwe.cf.ac.uk/id/eprint/49905

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