Store-Operated Calcium Channel and Cancer

Abstract

The increase of intracellular Ca2+ concentration is an important mechanism that regulates a variety of physiological processes ranging from exocytosis to gene regulation and cell proliferation [1]. Calcium release from intracellular stores (mainly endoplasmic reticulum, ER) or calcium entry through calcium channels can be used by cells to evoke a higher level of cytosolic Ca2+ concentration. In non-excitable cells, a major pathway for Ca2+ influx is via store-operated Ca2+ channels (also known as capacitative calcium entry) [2]. The concept of Store-operated calcium (SOC) channel was first proposed by James Putney in 1986 [3]. In this model, the depletion of intracellular calcium stores triggers calcium entry across the plasma membrane. In 1992, Hoth & Penner identified the presence of this a Ca2+ release-activated Ca2+ current (CRAC) [4]. Using RNA interference (RNAi)-based approaches, STIM1, an intracellular calcium sensor, was found in 2005 [5, 6]. One year later, Orai1 (CRACM1) was discovered as an essential component of store-operated calcium channel in T cells and mast cells [7, 8]. The role of Ca2+ in cell motility has been known for a long time. There is evicence that Ca2+ influx is more important than Ca2+ release in the migration of fibroblast and breast cancer cells [9, 10].