期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
卷 1833, 期 7, 页码 1732-1744出版社
ELSEVIER
DOI: 10.1016/j.bbamcr.2012.12.011
关键词
Parathyroid adenoma; Colorectal cancer; Breast cancer; Prostate cancer; Systems biology; Ligand-biased signalling
资金
- Marie Curie Initial Training Network Multifaceted CaSR [FP7-264663]
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-o(2+)) 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-o(2+). 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. (C) 2012 Elsevier B.V. All rights reserved.
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