Ribosomal protein S6 promotes stem‐like characters in glioma cells
Ribosomal protein S6 promotes stem‐like characters in glioma cells
复制标题
核糖体蛋白S6促进神经胶质瘤细胞的干细胞样特征
DOI：
10.1111/cas.14399
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发表时间：
2020
期刊：
影响因子：
5.7
通讯作者：
Jono Hirofumi
中科院分区：
文献类型：
--
作者：
Shirakawa Yuki;Hide Takuichiro;Yamaoka Michiko;Ito Yuki;Ito Naofumi;Ohta Kunimasa;Shinojima Naoki;Mukasa Akitake;Saito Hideyuki;Jono Hirofumi
多形性胶质母细胞瘤(GBM)是一种发生于成人大脑白质的致命性脑肿瘤，含有少量的GBM干细胞(GSCs)，可能导致化疗耐药和肿瘤复发。然而，GSCs的发病和维持机制在很大程度上仍不清楚。最近的一项研究报道，将核糖体和核糖体蛋白整合到体细胞中，促进了向多能性方向的谱系转分化。本研究旨在通过研究40S核糖体蛋白S6(RPS6)来探讨GBM细胞获得干性的机制。RPS6在高级别胶质瘤中显著上调，并定位于GBM组织中血管周围、坏死周围和边缘的壁龛。SiRNA介导的RPS6基因敲除显著抑制了GSCs的特性，包括其肿瘤球位和GSC标志物的表达；STAT3在GBM细胞中下调。RPS6过表达可增强GSCs的肿瘤生长潜能，这种作用可被STAT3抑制剂(AG490)减弱。在不同级别的胶质瘤中，RPS6和SOX2的表达均显著相关。免疫组织化学数据表明，RPS6在GSC生态位中占主导地位，与常春藤GAP数据库的数据一致。此外，RPS6和其他核糖体蛋白在该数据库中的GSC优势区上调。目前的结果表明，在GSC的生态位中，核糖体蛋白在GSC的发育和维持中起着关键作用，并与化疗放射耐药和GBM复发有关。
Glioblastoma multiforme (GBM), a lethal brain tumor developing in the white matter of the adult brain, contains a small population of GBM stem cells (GSCs), which potentially cause chemotherapeutic resistance and tumor recurrence. However, the mechanisms underlying the pathogenesis and maintenance of GSCs remain largely unknown. A recent study reported that incorporation of ribosomes and ribosomal proteins into somatic cells promoted lineage trans‐differentiation toward multipotency. This study aimed to investigate the mechanism underlying stemness acquisition in GBM cells by focusing on 40S ribosomal protein S6 (RPS6). RPS6 was significantly upregulated in high‐grade glioma and localized at perivascular, perinecrotic, and border niches in GBM tissues. siRNA‐mediated RPS6 knock‐down significantly suppressed the characteristics of GSCs, including their tumorsphere potential and GSC marker expression; STAT3 was downregulated in GBM cells. RPS6 overexpression enhanced the tumorsphere potential of GSCs and these effects were attenuated by STAT3 inhibitor (AG490). Moreover, RPS6 expression was significantly correlated with SOX2 expression in different glioma grades. Immunohistochemistry data herein indicated that RPS6 was predominant in GSC niches, concurrent with the data from IVY GAP databases. Furthermore, RPS6 and other ribosomal proteins were upregulated in GSC‐predominant areas in this database. The present results indicate that, in GSC niches, ribosomal proteins play crucial roles in the development and maintenance of GSCs and are clinically associated with chemoradioresistance and GBM recurrence.
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影响因子：
158.5
作者：
Stupp, R;Mason, WP;Ryan, G
通讯作者：
Ryan, G
影响因子：
50.3
作者：
Bromberg J;Wang TC
通讯作者：
Wang TC
影响因子：
--
作者：
Leidgens V;Proske J;Rauer L;Moeckel S;Renner K;Bogdahn U;Riemenschneider MJ;Proescholdt M;Vollmann-Zwerenz A;Hau P;Seliger C
通讯作者：
Seliger C
影响因子：
18.4
作者：
Hambardzumyan D;Bergers G
通讯作者：
Bergers G
通过核糖体转分化人类体细胞通过核糖体转分化人类体细胞
DOI：
--
发表时间：
2019
期刊：
影响因子：
--
作者：
佐々木悠;西山晃;川瀬航;西村晃成;黒滝大翼;関田洋一;木村透;田村智彦;太田 訓正;田村智彦;太田 訓正
通讯作者：
太田 訓正