Involvement of store-operated calcium signaling in EGF-mediated COX-2 gene activation in cancer cells

STIM and Orai proteins as novel targets for cancer therapy. A Review in the Theme: Cell and Molecular Processes in Cancer Metastasis

“…Higher STIM1 expression correlated with the increased tumor size, tumor invasion, and metastasis (108). Interestingly, the same group had previously reported that EGF-mediated activation of proinflammatory and prometastatic gene cyclooxygenase2 (COX-2) requires STIM1-Orai1-mediated SOCE (107). Further, the authors demonstrated that STIM1 regulates colon cancer cell migration via selectively regulating COX-2 but not cyclooxygenase1 (COX-1) expression at the transcriptional level (108).…”

Involvement of L‐type Ca2+ channel and toll‐like receptor‐4 in nickel‐induced interleukin‐8 gene expression

“…Considering the concept of metal ion mimicry, calcium channels are very likely to be transducers of nickel. Indeed, calcium channels have been considered as important mediators of inflammatory gene activation Wang et al, 2012;Yang et al, 2013;Guo et al, 2013). In addition, pretreatment with the calcium channel blockers, verapamil and nicardipine, decreased nickel uptake by 20% (Funakoshi et al, 1997).…”

Calcium signaling and cell proliferation

“…Growing evidence implicates a robust SOCE response is responsible for the stimulation of proliferation, survival and invasion of cancerous cells like melanoma [49], breast [50], colon [51], lung [52] and hepatocellular carcinoma cells [53]. For instance, one of these first reports demonstrated that STIM1 protein activation in the ER of melanoma cells was capable of triggering Ca 2+ influx and Ca 2+ /calmodulin (CaM)-dependent activation of the proto-oncogene tyrosine-protein kinase (Src)/protein phosphatase 2 (PP2A)/protein kinase B (PKB) cascade [54], a critical cascade for melanoma malignancy.…”