Calcium Signalling

Cancer-causing mutations disrupt the homeostasis of normal cells, and remodel it to promote survival of the cancerous cells. Among many factors that control cellular homeostasis, the calcium ion (Ca2+) is a vital second messenger in the cell, whose concentration is tightly regulated, such that it generates cellular signals in response to external stimuli. Utilizing Ca2+signal pathways, metastatic cancer cells develop an enhanced propensity to migrate, and effectively detach from the tumour, enter the circulation system, and re-establish secondary growth in distant organs. The Ca2+ signalling pathway responsible for cancer metastasis appears to involve Orai1, and stromal interaction molecule 1 (STIM1), which are downstream of the inositol 1,4,5-trisphosphate (IP3) receptor (IP3R), G-protein-coupled receptors and receptor tyrosine kinases. Recent studies have revealed that Ca2+ high/STIM2 low expression. These molecular alterations in cancer cells lead to remodeling of intracellular Ca2+ homeostasis, resulting in altered gene expression in the cell. Interestingly, a point mutation of Orai1 (R91W) was identified in patients with the severe combined immune deficiency syndrome (SCID) and this mutation was found to impair Ca2+-release-activated Ca2+ (CRAC) activity. In order to understand how the concentration of 2+ in the cell is regulated in both a spatial and a temporal manner, and how this affects gene expression in cancer cells, we need to better understand the roles and precise regulatory mechanisms of various 2+ transporters (i.e., Ca2+ channels and Ca2+ pumps).

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