STIM1-mediated calcium signalling in cancer: Its relation to tumour aggressiveness and therapeutic horizons

Abstract

Calcium ions (Ca²⁺), pivotal regulators of tumour progression, drive cancer metastasis and therapy resistance via STIM1-mediated store-operated calcium entry (SOCE). This review focuses on the role of STIM1 and SOCE-mediated calcium signalling in various cancer types, with particular emphasis on oral cancer as a key area of our research, and future research directions in these areas are proposed. Specifically, this review reveals the mechanism by which the STIM1/Orai1 complex activates calmodulin (CaM)-dependent effectors to promote epithelial–mesenchymal transition (EMT) and remodelling of the cytoskeleton and immunosuppressive microenvironment. Clinically, STIM1 overexpression is correlated with advanced tumour stage, chemoresistance, and a poor prognosis, highlighting its dual role as a prognostic biomarker and therapeutic target. Although preclinical studies have demonstrated that calcium release-activated calcium (CRAC) channel inhibitors suppress tumour growth, challenges such as calcium signalling complexity and tissue-specific toxicity persist. Future research should integrate emerging technologies and systematic approaches to clarify the mechanisms underlying the dynamic regulation of calcium signalling networks, which will ultimately accelerate their clinical translation and therapeutic application.