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TreasureVibe
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ABSTRACT The GTPase Ras is a molecular switch engaged downstream of G-protein-coupled receptors and receptor tyrosine kinases that controls multiple cell-fate-determining signalling pathways. Ras signalling is frequently deregulated in cancer, underlying associated changes in cell phenotype. Although Ca2+ signalling pathways control some overlapping functions with Ras, and altered Ca2+ signalling pathways are emerging as important players in oncogenic transformation, how Ca2+ signalling is remodelled during transformation and whether it has a causal role remains unclear. We have investigated Ca2+ signalling in two human colorectal cancer cell lines and their isogenic derivatives in which the allele encoding oncogenic K-Ras (G13D) was deleted by homologous recombination. We show that agonist-induced Ca2+ release from the endoplasmic reticulum (ER) intracellular Ca2+ stores is enhanced by loss of K-RasG13D through an increase in the Ca2+ content of the ER store and a modification of the abundance of inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) subtypes. Consistently, uptake of Ca2+ into mitochondria and sensitivity to apoptosis was enhanced as a result of K-RasG13D loss. These results suggest that suppression of Ca2+ signalling is a common response to naturally occurring levels of K-RasG13D, and that this contributes to a survival advantage during oncogenic transformation. KEY WORDS: K-R
RESEARCH ARTICLE Oncogenic K-Ras suppresses IP3-dependent Ca2+ release through remodelling of the isoform composition of IP3Rs and ER luminal Ca2+ levels in colorectal cancer cell lines Cristina Pierro, Simon J. Cook, Thomas C. F. Foets, Martin D. Bootman* and H. Llewelyn Roderick 2014
http://jcs.biologists.org/content/joces/127/7/1607.full.pdf
RESEARCH ARTICLE Oncogenic K-Ras suppresses IP3-dependent Ca2+ release through remodelling of the isoform composition of IP3Rs and ER luminal Ca2+ levels in colorectal cancer cell lines Cristina Pierro, Simon J. Cook, Thomas C. F. Foets, Martin D. Bootman* and H. Llewelyn Roderick 2014
http://jcs.biologists.org/content/joces/127/7/1607.full.pdf