SATB2 drives glioblastoma growth by recruiting CBP to promote FOXM1 expression in glioma stem cells.
SATB2 drives glioblastoma growth by recruiting CBP to promote FOXM1 expression in glioma stem cells.
复制标题
DOI：
10.15252/emmm.202012291
复制
发表时间：
2020-12-07
影响因子：
11.1
通讯作者：
Bao S
中科院分区：
文献类型：
--
作者：
Tao W;Zhang A;Zhai K;Huang Z;Huang H;Zhou W;Huang Q;Fang X;Prager BC;Wang X;Wu Q;Sloan AE;Ahluwalia MS;Lathia JD;Yu JS;Rich JN;Bao S
核基质相关蛋白（NMPs）通过与DNA的基质附着区（MARs）结合，在调节染色质组织和基因转录中发挥关键作用。然而，NMPs在胶质母细胞瘤（GBM）进展中的功能意义仍不清楚。在这里，我们表明，特殊的富含AT的结合蛋白-2（SATB 2），一个关键的NMPs，招募组蛋白乙酰转移酶CBP，以促进FOXM 1介导的细胞增殖和GBM的肿瘤生长。SATB 2优先由GBM中的胶质瘤干细胞（GSC）表达。破坏SATB 2通过下调参与细胞增殖程序的关键基因的表达显著抑制GSC增殖和GBM恶性生长。SATB 2通过与FOXM 1基因座的MAR序列结合并将CBP募集至MAR来激活FOXM 1表达以促进GSC增殖。重要的是，CBP抑制剂C646对SATB 2/CBP转录活性的药理学抑制抑制体外GSC增殖和体内GBM生长。我们的研究揭示了SATB 2/CBP介导的转录调控在GBM生长中的关键作用，表明靶向SATB 2/CBP可以有效地改善GBM治疗。核基质相关蛋白（NMPs）的异常表达已被证明与各种人类癌症中的肿瘤生长相关。这项研究表明，SATB 2，一个关键的NMP，及其共激活剂CBP关键性地促进胶质母细胞瘤（GBM）的生长，这表明SATB 2/CBP是一个治疗靶点。
Nuclear matrix‐associated proteins (NMPs) play critical roles in regulating chromatin organization and gene transcription by binding to the matrix attachment regions (MARs) of DNA. However, the functional significance of NMPs in glioblastoma (GBM) progression remains unclear. Here, we show that the Special AT‐rich Binding Protein‐2 (SATB2), one of crucial NMPs, recruits histone acetyltransferase CBP to promote the FOXM1‐mediated cell proliferation and tumor growth of GBM. SATB2 is preferentially expressed by glioma stem cells (GSCs) in GBM. Disrupting SATB2 markedly inhibited GSC proliferation and GBM malignant growth by down‐regulating expression of key genes involved in cell proliferation program. SATB2 activates FOXM1 expression to promote GSC proliferation through binding to the MAR sequence of FOXM1 gene locus and recruiting CBP to the MAR. Importantly, pharmacological inhibition of SATB2/CBP transcriptional activity by the CBP inhibitor C646 suppressed GSC proliferation in vitro and GBM growth in vivo. Our study uncovers a crucial role of the SATB2/CBP‐mediated transcriptional regulation in GBM growth, indicating that targeting SATB2/CBP may effectively improve GBM treatment. Aberrant expression of nuclear matrix‐associated proteins (NMPs) has been shown to associate with tumor growth in various human cancers. This study shows that SATB2, a key NMP, and its coactivator CBP critically contribute to glioblastoma (GBM) growth, suggesting SATB2/CBP is a therapeutic target.
登录
查看更多内容
FOXM1上皮卵巢癌中FOXM1过表达的遗传决定因素以及对细胞周期进程的功能贡献。
影响因子：
--
作者：
Barger CJ;Zhang W;Hillman J;Stablewski AB;Higgins MJ;Vanderhyden BC;Odunsi K;Karpf AR
通讯作者：
Karpf AR
miR-211 通过下调 SATB2 抑制肝细胞癌。
影响因子：
--
作者：
Jiang G;Cui Y;Yu X;Wu Z;Ding G;Cao L
通讯作者：
Cao L
影响因子：
5.3
作者：
Diaz-Alonso, Javier;Aguado, Tania;Galve-Roperh, Ismael
通讯作者：
Galve-Roperh, Ismael
影响因子：
5.2
作者：
Joshi, Kaushal;Banasavadi-Siddegowda, Yeshavanth;Mo, Xiaokui;Kim, Sung-Hak;Mao, Ping;Kig, Cenk;Nardini, Diana;Sobol, Robert W.;Chow, Lionel M. L.;Kornblum, Harley I.;Waclaw, Ronald;Beullens, Monique;Nakano, Ichiro
通讯作者：
Nakano, Ichiro
影响因子：
3.4
作者：
Britanova, O;Akopov, S;Tarabykin, V
通讯作者：
Tarabykin, V