Department of Molecular Pathobiology, New York University College of Dentistry, New York, NY 10010, USA.
NYU Dentistry Translational Research Center, Department of Oral and Maxillofacial Surgery, New York University College of Dentistry, New York, NY 10010, USA.
Sci Signal. 2023 Sep 5;16(801):eadf9535. doi: 10.1126/scisignal.adf9535.
Oral cancer causes pain associated with cancer progression. We report here that the function of the Ca channel ORAI1 is an important regulator of oral cancer pain. was highly expressed in tumor samples from patients with oral cancer, and ORAI1 activation caused sustained Ca 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 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.
口腔癌引起与癌症进展相关的疼痛。我们在这里报告，Ca 通道 ORAI1 的功能是口腔癌痛的一个重要调节因子。 在口腔癌患者的肿瘤样本中高度表达，并且 ORAI1 的激活导致人口腔癌细胞中持续的 Ca 内流。RNA-seq 分析表明，ORAI1 调节许多编码口腔癌标志物的基因，如金属蛋白酶（MMPs）和痛觉调节剂。与对照细胞相比，缺乏 的口腔癌细胞形成的肿瘤较小，当接种到小鼠爪子中时，引起的痛觉过敏减少。暴露于三叉神经节神经元的 MMP1 会引起动作电位增加。这些数据表明 ORAI1 在口腔癌进展和疼痛中起重要作用，可能通过控制 MMP1 的丰度。
