CD59 Regulation by SOX2 Is Required for Epithelial Cancer Stem Cells to Evade Complement Surveillance.
CD59 Regulation by SOX2 Is Required for Epithelial Cancer Stem Cells to Evade Complement Surveillance.
复制标题
SOX2 对 CD59 的调节是上皮癌干细胞逃避补体监视所必需的。
DOI：
10.1016/j.stemcr.2016.11.008
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发表时间：
2017-01-10
影响因子：
5.9
通讯作者：
Hu W
中科院分区：
文献类型：
--
作者：
Chen J;Ding P;Li L;Gu H;Zhang X;Zhang L;Wang N;Gan L;Wang Q;Zhang W;Hu W
肿瘤干细胞（CSCs）与治疗耐药和转移高度相关。CSCs与多种免疫成分之间的相互作用是肿瘤存活所必需的。然而，csc对补充监测的反应尚不清楚。在这里，我们使用从乳腺肿瘤细胞系和肺腺癌细胞系制备的干细胞样球体形成细胞，我们发现CD59上调以保护CSCs免受补体依赖性细胞毒性的影响。CD59沉默显著增强补体破坏，完全抑制csc移植裸鼠的肿瘤发生。此外，我们发现SOX2上调上皮性CSCs中的CD59。此外，我们发现SOX2调节mCd59b的转录，导致小鼠睾丸精原干细胞中mCd59b的选择性丰富。因此，我们证明了SOX2对CD59的调控是干细胞逃避补体监视所必需的。这一发现强调了补体监测在消除CSCs中的重要性，并可能表明CD59是癌症治疗的潜在靶点。SOX2负责干细胞中CD59的上调SOX2调节小鼠睾丸精原干细胞中CD59和mCD59b的选择性表达，但不调节其他膜调节蛋白，这些蛋白在干细胞中被SOX2上调，并且需要逃避补体监视。CD59不足可能导致肿瘤生长几乎完全停止和肿瘤干细胞的发生丧失。
Cancer stem cells (CSCs) are highly associated with therapy resistance and metastasis. Interplay between CSCs and various immune components is required for tumor survival. However, the response of CSCs to complement surveillance remains unknown. Herein, using stem-like sphere-forming cells prepared from a mammary tumor and a lung adenocarcinoma cell line, we found that CD59 was upregulated to protect CSCs from complement-dependent cytotoxicity. CD59 silencing significantly enhanced complement destruction and completely suppressed tumorigenesis in CSC-xenografted nude mice. Furthermore, we identified that SOX2 upregulates CD59 in epithelial CSCs. In addition, we revealed that SOX2 regulates the transcription of mCd59b, leading to selective mCD59b abundance in murine testis spermatogonial stem cells. Therefore, we demonstrated that CD59 regulation by SOX2 is required for stem cell evasion of complement surveillance. This finding highlights the importance of complement surveillance in eliminating CSCs and may suggest CD59 as a potential target for cancer therapy. CD59 upregulation is required for stem cells evading complement surveillance SOX2 is responsible for CD59 upregulation in stem cells SOX2 regulates mCD59b selective expression in testis spermatogonial stem cells CD59 and mCD59b in mouse, but not other membrane regulatory proteins, are upregulated by SOX2 in stem cells and are required to evade complement surveillance. CD59 insufficiency may result in near-complete arrest of tumor growth and loss of tumorigenesis of cancer stem cells.