Store-Operated Calcium Entry As an Important Mechanism of Tumor Adaptation to an Aggressive Microenvironment.

Abstract

Calcium signaling ensures efficient cellular functioning; calcium homeostasis disruption leaves behind detrimental sequelae for the cell both under calcium excess and deficiency conditions. Malignant transformation is accompanied by significant alterations in the expression of the proteins critical for store-operated calcium entry, resulting in the dysregulation of calcium signaling. It is plausible that a remodeling of intracellular signal transduction pathways in cancer cells is required in order to accelerate metabolic processes, as well as fuel further tumor growth and invasion. Meanwhile, fine-tuning of calcium signaling is observed under both normal and pathological conditions. In this context, research into the changes accompanying signal transduction within the tumor microenvironment is a key aspect of the investigation of the role of calcium signaling in tumor development. Factors characteristic of the tumor microenvironment were shown to have a significant effect on the function of calcium channels and the proteins that regulate calcium signaling. Major, adverse microenvironmental factors, such as acidification, elevated levels of reactive oxygen species and hypoxia, have a bearing on the store-operated calcium entry. It is crucial to understand whether changes in the expression of the key SOCE components represent an adaptation to the microenvironment or a result of carcinogenesis.