Store operated calcium entry is altered by the inhibition of receptors tyrosine kinase
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Noémie Emeriau1, Marie de Clippele1, Philippe Gailly1,* and Nicolas Tajeddine1,*
1Laboratory of Cell Physiology, Institute of Neuroscience, Université catholique de Louvain, Brussels, Belgium
*These authors share senior authorship
Nicolas Tajeddine, email: firstname.lastname@example.org
Keywords: store-operated calcium entry; EGFR; ErbB2; receptors tyrosine kinase; targeted therapies
Received: June 16, 2017 Accepted: February 28, 2018 Published: March 23, 2018
SOCE (Store-Operated Calcium Entry) is the main mechanism by which external Ca2+ enters into non-excitable cells after endoplasmic reticulum emptying. It is implicated in several processes such as proliferation and migration. Alterations in SOCE could initiate or support the development of hallmarks of cancer. In this project, we showed that disruption of the EGFR/ErbB2-dependent signalling by lapatinib and CP-724714, two inhibitors of the receptor tyrosine kinase (RTK), dramatically reduced the amplitude of the SOCE in breast cancer cells. LY294002 and MK2206, two inhibitors of the PI3K/Akt pathway, mimicked the effect of the inhibition of EGFR/ErbB2. In contrast, inhibitors of the MAPK pathway had no effect on SOCE. The involvement of EGFR/ErbB2 receptors and the PI3K/Akt pathway in the regulation of SOCE was confirmed in other cell lines derived from various cancer types. All these results showed that SOCE is positively regulated by the PI3K/Akt pathway and that this effect may be suppressed by the inhibition of the upstream RTKs. Inhibition of SOCE might therefore contribute to the anticancer effects of RTK inhibitors.
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