Store-operated Ca2+ entry (SOCE) is the major pathway of Ca2+ entry in mammalian cells, and regulates a variety of cellular functions including proliferation, motility, apoptosis, and death. Accumulating evidence has indicated that augmented SOCE is related to the generation and development of cancer, including tumor formation, proliferation, angiogenesis, metastasis, and antitumor immunity. Therefore, the development of compounds targeting SOCE has been proposed as a potential and effective strategy for use in cancer therapy. In this review, we summarize the current research on SOCE inhibitors and blockers, discuss their effects and possible mechanisms of action in cancer therapy, and induce a new perspective on the treatment of cancer.

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The aim of the study was to examine the mechanism of action of Lidan Granule (LDG) for the prevention of gallstones using a guinea pig model. One hundred guinea pigs were divided into five groups randomly: control (standard diet and saline), model [lithogenic diet (LD) and saline], LDG-H (LD and 2 g/kg of LDG), LDG-L (LD and 1 g/kg of LDG), and ursodeoxycholic acid (UDCA) (LD and UDCA) as the positive control. At 6 weeks, the rate of gallstone formation and weight of the adrenal gland were recorded and serum levels of inflammatory cytokines were measured. Levels of corticotrophin-releasing hormone (CRH) in the hypothalamus, adrenocorticotropic hormone (ACTH) in the hypophysis, and serum cortisol were determined. Bile components were tested with colorimetry. At 6 weeks, the rate of gallstone formation was significantly decreased in the LDG-H (14.29%) and LDG-L (21.43%) groups compared to the model group (81.25%; P<0.01). LDG treatment decreased the serum levels of interleukin (IL)-1, IL-6, and tumor necrosis factor-α (P<0.01). LDG decreased bile cholesterol and increased bile acid and phospholipid levels in the bile (P<0.01). LDG treatment recovered the function of the hypothalamic-pituitary-adrenal (HPA) axis by increasing the expression of CRH (P<0.01) and ACTH (P<0.05). LDG made the bile less lithogenic, improved the function of the HPA axis, and regulated the expression of inflammatory cytokines for the prevention of cholelithiasis.

Deregulated store‐operated calcium entry (SOCE) mediated by aberrant STIM1‐ORAI1 signaling is closely implicated in cancer initiation and progression. Here the authors report the identification of an alternatively spliced variant of STIM1, designated STIM1β, that harbors an extra exon to encode 31 additional amino acids in the cytoplasmic domain. STIM1β, highly conserved in mammals, is aberrantly upregulated in glioma tissues to perturb Ca2+ signaling. At the molecular level, the 31‐residue insertion destabilizes STIM1β by perturbing its cytosolic inhibitory domain and accelerating its activation kinetics to efficiently engage and gate ORAI calcium channels. Functionally, STIM1β depletion affects SOCE in glioblastoma cells, suppresses tumor cell proliferation and growth both in vitro and in vivo. Collectively, their study establishes a splicing variant‐specific tumor‐promoting role of STIM1β that can be potentially targeted for glioblastoma intervention.