Store-operated calcium (SOC) influx is the major calcium entry mechanism in non-excitable cells regulating a plethora of physiological and pathological processes. The internal store calcium sensor and plasma membrane pore-forming unit are recently identified to be Stim1 and Orai1, respectively. We were the first to demonstrate the critical roles of Stim1 and Orai1 in breast tumor cell migration and metastasis (Cancer Cell, 2009, 15:124). There are still a few important questions remained to be answer: Whether Stim1 and Orai1 play a role in the dissemination of other tumors? How do Stim1 and Orai1 dysregulate and reorganize actin cytoskeleton to promote tumor cell invasion and metastasis? Do Stim1 and Orai1 contribute to tumor progression in cancer patients? Our recent data suggested that Stim1 and Orai1 were important regulators of tumor cell migration and invasion in multiple tumors. SOC inhibitors block cell migration and invasion in all the tumors tested. Stim1 and Orai1 promote tumor cell invasion and degradation of extracellular matrix by promoting the formation of invadopodia. Stim1 and Orai1 regulate invadopodia formation through facilitating SOC calcium influx and activation of non-receptor tyrosine kinase Src. The activation of Src by SOC influx also contributes to anoikis resistance in tumor cells. We were able to further demonstrate that the expression levels of Stim1 correlate with tumor progression and metastasis in multiple solid tumors. Therefore, our data suggested that Stim1 overexpression in tumors may promote tumor metastasis through calcium influx and Src activation, which facilitate extracellular matrix degradation and promote anchorage-independent growth.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4317. doi:1538-7445.AM2012-4317