Sox2 expression involvement in the oncogenicity and radiochemoresistance of oral cancer stem cells
Sox2 expression involvement in the oncogenicity and radiochemoresistance of oral cancer stem cells
复制标题
DOI：
10.1016/j.oraloncology.2014.10.002
复制
发表时间：
2015-01-01
期刊：
影响因子：
4.8
通讯作者：
Yu, Cheng-Chia
中科院分区：
文献类型：
--
作者：
Chou, Ming-Yung;Hu, Fang-Wei;Yu, Cheng-Chia
目的：Sox2是一种高流动性的DNA结合蛋白，是一组关键的转录因子，参与维持未分化干细胞的多能性和自我更新。最近的一项研究进一步表明，癌症干细胞（CSCs）是放射化疗耐药的关键因素，也是口腔鳞状细胞癌（OSCC）进展的原因。本研究的目的是确定Sox2在口服CSCs放射化学敏感性中的新作用。方法：在体外和体内通过过表达或沉默Sox2来检测Sox2对OSCC致癌性和放化疗敏感性的作用。结果：最初，Sox2在OSCC细胞系和OSCC标本中表达升高。Sox2表达上调与OSCC患者生存预后差相关。研究表明，过表达Sox2可增强OSCC细胞的侵袭性、非锚定生长和异种移植致瘤性。将Sox2靶向OSCC的球状细胞（SC）和ALDH1+CD44+细胞，可显著抑制其csc和致瘤能力。研究发现，SOX2在OSCC-SC中的下调可抑制侵袭性并降低上皮-间质转化（EMT）特性。此外，沉默Sox2可有效抑制耐药和抗凋亡基因的表达，增加细胞对放疗联合顺铂治疗的敏感性。最后，在oscc - sc移植免疫功能低下小鼠中，靶向Sox2与放疗、顺铂联合使用的体内治疗效果协同抑制肿瘤发生，提高生存率。结论：Sox2介导的CSCs性质与EMT调控和Sox2作为OSCC治疗靶点有关。(C) 2014 Elsevier Ltd.版权所有。
Objectives: Sox2, a high-mobility-group DNA binding protein, is part of the key set of transcription factors that are involved in the maintenance of pluripotency and self-renewal in undifferentiated stem cells. A recent study has further suggested cancer stem cells (CSCs) are key contributors to radiochemoresistance and are responsible for oral squamous cell carcinoma (OSCC) progression. The aim of this study was to determine the emerging role of Sox2 in radiochemosensitivity of oral CSCs.Methods: We determined the function of Sox2 on oncogenicity and radiochemosensitivity of OSCC by overexpression or silencing Sox2 in vitro and in vivo.Results: Initially, Sox2 expression was increased in OSCC cell lines and OSCC specimens. Upregulated Sox2 is correlated with poor survival outcome of OSCC patients. Overexpression of Sox2 was demonstrated to enhance invasiveness, anchorage-independent growth, xenotransplantation tumourigenicity in OSCC cells. Targeting Sox2 to spheroid cells (SC) and ALDH1+CD44+ cells from OSCC significantly inhibited their CSCs and tumorigenic abilities. Down regulation of SOX2 in OSCC-SC was found to repress invasiveness and diminish epithelail-mesenchymal transition (EMT) traits. Furthermore, silencing Sox2 effectively suppressed the expression of drug-resistance and anti-apoptotic genes and increased the sensitivity of the cells to radiation combined cisplatin treatment. Finally, the in vivo therapeutic efficacy of targeting Sox2 synergistically suppressed tumorigenesis and improved the survival rate when used in combination with radiotherapy and cisplatin in OSCC-SC-transplanted immunocompromised mice.Conclusion: Sox2-mediated CSCs property is associated with the regulation of EMT and Sox2 s as therapeutic target in OSCC. (C) 2014 Elsevier Ltd. All rights reserved.