The NSL Chromatin-Modifying Complex Subunit KANSL2 Regulates Cancer Stem-like Properties in Glioblastoma That Contribute to Tumorigenesis.
The NSL Chromatin-Modifying Complex Subunit KANSL2 Regulates Cancer Stem-like Properties in Glioblastoma That Contribute to Tumorigenesis.
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DOI：
10.1158/0008-5472.can-15-3159
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发表时间：
2016-09-15
期刊：
影响因子：
11.2
通讯作者：
Perez-Castro C
中科院分区：
文献类型：
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作者：
Ferreyra Solari NE;Belforte FS;Canedo L;Videla-Richardson GA;Espinosa JM;Rossi M;Serna E;Riudavets MA;Martinetto H;Sevlever G;Perez-Castro C
KANSL2是非特异性致死(NSL)染色质修饰复合体的一个完整的亚基，它对胚胎干细胞的表观遗传程序有贡献。在这项研究中，我们报道了KANSL2在胶质母细胞瘤(GBM)干性调节中的作用，胶质母细胞瘤的特征是与治疗抵抗和疾病复发相关的异质肿瘤干细胞。KANSL2在癌细胞中表达上调，主要在肿瘤的血管周围区域。RNAi介导的KANSL2沉默GBM细胞在小鼠异种移植模型中的致瘤能力。在临床标本中，我们发现KANSL2的表达水平与GBM干细胞样细胞群体中的干性标记相关。机制研究表明，KANSL2调节细胞的自我更新，这与影响干性转录因子Pou5f1的表达有关。RNAi介导的Pou5f1沉默降低了KANSL2的水平，将这两个基因与GBM细胞的干性控制联系在一起。总之，我们的发现表明KANSL2对GBM中的干细胞群起调节作用，将其定义为临床使用的候选GBM生物标记物。
KANSL2 is an integral subunit of the Non-Specific Lethal (NSL) chromatin-modifying complex which contributes to epigenetic programs in embryonic stem cells. In this study, we report a role for KANSL2 in regulation of stemness in glioblastoma (GBM), which is characterized by heterogeneous tumor stem-like cells associated with therapy resistance and disease relapse. KANSL2 expression is upregulated in cancer cells, mainly at perivascular regions of tumors. RNAi-mediated silencing of KANSL2 in GBM cells impairs their tumorigenic capacity in mouse xenograft models. In clinical specimens, we found that expression levels of KANSL2 correlate with stemness markers in GBM stem-like cell populations. Mechanistic investigations showed that KANSL2 regulates cell self-renewal, which correlates with effects on expression of the stemness transcription factor POU5F1. RNAi-mediated silencing of POU5F1 reduced KANSL2 levels, linking these two genes to stemness control in GBM cells. Together, our findings indicate that KANSL2 acts to regulate the stem cell population in GBM, defining it as a candidate GBM biomarker for clinical use.