STIM1 in tumor cell death: angel or devil?

AbstractStromal interaction molecule 1 (STIM1) is involved in mediating the store-operated Ca2+ entry (SOCE), driving the influx of the intracellular second messenger calcium ion (Ca2+), which is closely associated with tumor cell proliferation, metastasis, apoptosis, autophagy, metabolism and immune processes. STIM1 is not only regulated at the transcriptional level by NF-κB and HIF-1, but also post-transcriptionally modified by miRNAs and degraded by ubiquitination. Recent studies have shown that STIM1 or Ca2+ signaling can regulate apoptosis, autophagy, pyroptosis, and ferroptosis in tumor cells and act discrepantly in different cancers. Furthermore, STIM1 contributes to resistance against antitumor therapy by influencing tumor cell death. Further investigation into the mechanisms through which STIM1 controls other forms of tumor cell death could aid in the discovery of novel therapeutic targets. Moreover, STIM1 has the ability to regulate immune cells within the tumor microenvironment. Here, we review the basic structure, function and regulation of STIM1, summarize the signaling pathways through which STIM1 regulates tumor cell death, and propose the prospects of antitumor therapy by targeting STIM1.