Inhibition of store-operated Ca2+ entry suppresses EGF-induced migration and eliminates extravasation from vasculature in nasopharyngeal carcinoma cell

• It was demonstrated that SOCE is a predominant Ca2+ signaling for NPC cell metastasis.
• A zebrafish hematogenous metastasis model was recruited for the investigation of NPC cell metastasis.
• For the first time, the dynamic extravasation of NPC cells from vasculature was visually observed.

Store-operated Ca2+ entry (SOCE) mediates Ca2+ responses evoked by extracellular signaling molecules to promote increases in cytosolic Ca2+, thereby triggering downstream signal transduction. Here we demonstrated that either the pharmacological blockage of Ca2+ influx through SOCE or the knockdown of Orai1, a key molecule of SOCE, suppressed the epidermal growth factor-induced migration by disturbing Ca2+ signaling in nasopharyngeal carcinoma (NPC) cell. Furthermore, Orai1 depletion led to a delayed cell attachment to the extracellular matrix surface in vitro and eliminated the extravasation of microinjected cells from vasculature in a zebrafish hematogenous metastasis model. Our findings thus indicate that SOCE acts as a predominant Ca2+ signaling involved in NPC cell metastasis, and may serve as a candidate target for anti-metastasis therapy in NPC.