Orai3 Calcium Channel Contributes to Oral/Oropharyngeal Cancer Stemness through the Elevation of ID1 Expression.
Orai3 Calcium Channel Contributes to Oral/Oropharyngeal Cancer Stemness through the Elevation of ID1 Expression.
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DOI：
10.3390/cells12182225
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发表时间：
2023-09-07
期刊：
影响因子：
6
通讯作者：
Shin, Ki-Hyuk
中科院分区：
文献类型：
--
作者：
Nguyen, Anthony;Sung, Youngjae;Lee, Sung Hee;Martin, Charlotte Ellen;Srikanth, Sonal;Chen, Wei;Kang, Mo K.;Kim, Reuben H.;Park, No-Hee;Gwack, Yousang;Kim, Yong;Shin, Ki-Hyuk
越来越多的证据表明，细胞内钙（Ca2+）水平及其调节蛋白在正常干细胞增殖和分化中起着重要作用。癌症干细胞样细胞（Cancer stem-like cells, CSCs）是癌细胞的亚群，它们保留了与干细胞相似的特征，并在癌症进展中发挥重要作用。最近的研究报道，Orai3钙通道在人类癌症中起致癌作用。然而，其在csc中的作用仍未得到充分探索。在这项研究中，我们探讨了Orai3在口腔/口咽鳞状细胞癌（OSCC）进展和干性中的作用。在OSCC的进展过程中，Orai3的表达呈逐步增强的趋势。值得注意的是，Orai3在OSCC的CSC群体中高度富集。异位Orai3在非致瘤性永生化口腔上皮细胞中的表达增加了细胞内Ca2+水平，获得恶性生长和CSC特性。相反，在OSCC细胞中沉默内源性Orai3可抑制CSC表型，表明Orai3在CSC调控中起关键作用。此外，Orai3显著提高了干性转录因子DNA结合1抑制剂（ID1）的表达。Orai3和ID1在CSC中的表达高于非CSC，这表明Orai3/ID1轴在CSC调控中的功能重要性。此外，在异位Orai3过表达和OSCC的细胞中，ID1的抑制消除了CSC表型。我们的研究表明，Orai3在OSCC中是一种新的功能性CSC调节因子，并进一步表明Orai3通过上调ID1促进OSCC的癌变，从而在OSCC中发挥致癌作用。
Emerging evidence indicates that intracellular calcium (Ca2+) levels and their regulatory proteins play essential roles in normal stem cell proliferation and differentiation. Cancer stem-like cells (CSCs) are subpopulations of cancer cells that retain characteristics similar to stem cells and play an essential role in cancer progression. Recent studies have reported that the Orai3 calcium channel plays an oncogenic role in human cancer. However, its role in CSCs remains underexplored. In this study, we explored the effects of Orai3 in the progression and stemness of oral/oropharyngeal squamous cell carcinoma (OSCC). During the course of OSCC progression, the expression of Orai3 exhibited a stepwise augmentation. Notably, Orai3 was highly enriched in CSC populations of OSCC. Ectopic Orai3 expression in non-tumorigenic immortalized oral epithelial cells increased the intracellular Ca2+ levels, acquiring malignant growth and CSC properties. Conversely, silencing of the endogenous Orai3 in OSCC cells suppressed the CSC phenotype, indicating a pivotal role of Orai3 in CSC regulation. Moreover, Orai3 markedly increased the expression of inhibitor of DNA binding 1 (ID1), a stemness transcription factor. Orai3 and ID1 exhibited elevated expression within CSCs compared to their non-CSC counterparts, implying the functional importance of the Orai3/ID1 axis in CSC regulation. Furthermore, suppression of ID1 abrogated the CSC phenotype in the cell with ectopic Orai3 overexpression and OSCC. Our study reveals that Orai3 is a novel functional CSC regulator in OSCC and further suggests that Orai3 plays an oncogenic role in OSCC by promoting cancer stemness via ID1 upregulation.
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ORAI1有助于在前列腺癌细胞中建立抗凋亡的表型。
影响因子：
9
作者：
通讯作者：
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影响因子：
--
作者：
Benzerdjeb N;Sevestre H;Ahidouch A;Ouadid-Ahidouch H
通讯作者：
Ouadid-Ahidouch H
影响因子：
--
作者：
Lee, Sung Hee;Kieu, Calvin;Shin, Ki-Hyuk
通讯作者：
Shin, Ki-Hyuk
DOI：
10.1016/j.bbamcr.2021.119023
发表时间：
2021-04-23
影响因子：
5.1
作者：
Dubois, Charlotte;Kondratska, Kateryna;Prevarskaya, Natalia
通讯作者：
Prevarskaya, Natalia
DOI：
10.4049/jimmunol.1100847
发表时间：
2011-10-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kim KD;Srikanth S;Yee MK;Mock DC;Lawson GW;Gwack Y
通讯作者：
Gwack Y