IADR Abstract Archives
Orai3 Promotes OSCC Tumorigenesis and Cancer Stemness via ID1 Activation
Objectives: Ion channels, such as calcium channels, govern a vital role in physiology by regulating cellular processes such as cell proliferation, differentiation, and death. Orai3 calcium channels are involved in neoplastic processes including metastasis, chemoresistance, and apoptosis resistance in colorectal and breast cancer. However, the role of Orai3 calcium channels in oral carcinogenesis remains unexplored.
Methods: To investigate the role of Orai3 in oral carcinogenesis, we examined the level of Orai3 in normal, precancerous, and cancer cells by using multiple expression analyses. We also explored the mechanism by which Orai3 regulates oral carcinogenesis by performing gain-of and loss-of-function experiments.
Results: We demonstrated that Orai3 expression is elevated during oral carcinogenesis and further increased in cancer stem cells (CSCs) of oral squamous cell carcinoma (OSCC) compared to non-CSCs. Moreover, the ectopic expression of Orai3 converted non-tumorigenic immortalized oral epithelial cells to malignant cells that displayed CSC properties such as increased ALDH1 activity, self-renewal capacity, and migration ability. In addition, functional studies displayed genetic inhibition of Orai3 suppressed CSC phenotype. Furthermore, Orai3 upregulates DNA-binding protein inhibitor ID-1 (ID1), a key transcriptional regulator of cancer stemness. Genetic inhibition of ID1 suppressed CSC phenotype in the cells with ectopic Orai3 overexpression and OSCC, implying the importance of Orai3/ID1 axis on CSC phenotype.
Conclusions: Our study identifies Orai3 as a key molecular player in the role of cancer stemness, suggesting suppression of Orai3 may provide a therapeutic target opposing OSCC progression.
Methods: To investigate the role of Orai3 in oral carcinogenesis, we examined the level of Orai3 in normal, precancerous, and cancer cells by using multiple expression analyses. We also explored the mechanism by which Orai3 regulates oral carcinogenesis by performing gain-of and loss-of-function experiments.
Results: We demonstrated that Orai3 expression is elevated during oral carcinogenesis and further increased in cancer stem cells (CSCs) of oral squamous cell carcinoma (OSCC) compared to non-CSCs. Moreover, the ectopic expression of Orai3 converted non-tumorigenic immortalized oral epithelial cells to malignant cells that displayed CSC properties such as increased ALDH1 activity, self-renewal capacity, and migration ability. In addition, functional studies displayed genetic inhibition of Orai3 suppressed CSC phenotype. Furthermore, Orai3 upregulates DNA-binding protein inhibitor ID-1 (ID1), a key transcriptional regulator of cancer stemness. Genetic inhibition of ID1 suppressed CSC phenotype in the cells with ectopic Orai3 overexpression and OSCC, implying the importance of Orai3/ID1 axis on CSC phenotype.
Conclusions: Our study identifies Orai3 as a key molecular player in the role of cancer stemness, suggesting suppression of Orai3 may provide a therapeutic target opposing OSCC progression.