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NSL染色质修饰复合体亚基KANSL2调节胶质母细胞瘤中有助于肿瘤发生的癌症干细胞样特性。

The NSL Chromatin-Modifying Complex Subunit KANSL2 Regulates Cancer Stem-like Properties in Glioblastoma That Contribute to Tumorigenesis.

作者信息

Ferreyra Solari Nazarena E, Belforte Fiorella S, Canedo Lucía, Videla-Richardson Guillermo A, Espinosa Joaquín M, Rossi Mario, Serna Eva, Riudavets Miguel A, Martinetto Horacio, Sevlever Gustavo, Perez-Castro Carolina

机构信息

Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA)-CONICET -Partner Institute of the Max Planck Society, Buenos Aires, Argentina.

Laboratorio de Investigación aplicada a Neurociencias (LIAN), Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (FLENI), Buenos Aires, Argentina.

出版信息

Cancer Res. 2016 Sep 15;76(18):5383-94. doi: 10.1158/0008-5472.CAN-15-3159. Epub 2016 Jul 12.

DOI:10.1158/0008-5472.CAN-15-3159
PMID:27406830
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5026635/
Abstract

KANSL2 is an integral subunit of the nonspecific lethal (NSL) chromatin-modifying complex that 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. Cancer Res; 76(18); 5383-94. ©2016 AACR.

摘要

KANSL2是一种非特异性致死（NSL）染色质修饰复合物的组成亚基，该复合物参与胚胎干细胞的表观遗传程序。在本研究中，我们报告了KANSL2在胶质母细胞瘤（GBM）干性调控中的作用，GBM的特征是存在与治疗抗性和疾病复发相关的异质性肿瘤干细胞样细胞。KANSL2在癌细胞中表达上调，主要在肿瘤的血管周围区域。RNA干扰介导的GBM细胞中KANSL2沉默会损害其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志物相关。机制研究表明，KANSL2调节细胞自我更新，这与对干性转录因子POU5F1表达的影响相关。RNA干扰介导的POU5F1沉默降低了KANSL2水平，将这两个基因与GBM细胞中的干性控制联系起来。总之，我们的研究结果表明KANSL2在调节GBM中的干细胞群体中发挥作用，将其定义为一种可供临床使用的GBM候选生物标志物。癌症研究；76(18)；5383 - 5394。©2016美国癌症研究协会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5e4/5026635/2c0d67974e0c/nihms803507f6.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5e4/5026635/3ad3cd91c137/nihms803507f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5e4/5026635/29cf6ffa31d0/nihms803507f2.jpg
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