口腔癌会引起与癌症进展有关的疼痛。我们在这里报告，钙离子通道ORAI1的功能是口腔癌痛的重要调节因子。ORAI1在口腔癌患者的肿瘤样本中高度表达，并导致人类口腔癌细胞内持续的钙离子内流。RNA-seq分析显示，ORAI1调控了许多编码口腔癌标志物（如金属蛋白酶）和疼痛调节因子的基因。与对照组细胞相比，缺乏ORAI1的口腔癌细胞形成的肿瘤较小，并且接种至小鼠脚掌后引起的触觉过敏降低。三叉神经节神经元暴露于MMP1后，动作电位增加。这些数据表明ORAI1在口腔癌进展和疼痛中扮演了重要角色，可能通过控制MMP1的丰度来实现。

Oral cancer causes pain associated with cancer progression. We report here that the function of the Ca2+ channel ORAI1 is an important regulator of oral cancer pain. ORAI1 was highly expressed in tumor samples from patients with oral cancer, and ORAI1 activation caused sustained Ca2+ influx in human oral cancer cells. RNA-seq analysis showed that ORAI1 regulated many genes encoding oral cancer markers such as metalloproteases (MMPs) and pain modulators. Compared with control cells, oral cancer cells lacking ORAI1 formed smaller tumors that elicited decreased allodynia when inoculated into mouse paws. Exposure of trigeminal ganglia neurons to MMP1 evoked an increase in action potentials. These data demonstrate an important role of ORAI1 in oral cancer progression and pain, potentially by controlling MMP1 abundance.