RBPJ is a novel target for rhabdomyosarcoma therapy.
RBPJ is a novel target for rhabdomyosarcoma therapy.
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DOI：
10.1371/journal.pone.0039268
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Komiya S
中科院分区：
文献类型：
--
作者：
Nagao H;Setoguchi T;Kitamoto S;Ishidou Y;Nagano S;Yokouchi M;Abematsu M;Kawabata N;Maeda S;Yonezawa S;Komiya S
Notch通路在胎儿和出生后发育期间调节广泛的细胞命运决定和分化过程。此外，Notch通路在控制肿瘤发生中起重要作用。然而，RBPJ（Notch途径中的转录因子）在肿瘤发展中的作用在很大程度上是未知的。在这项研究中，我们专注于RBPJ在横纹肌肉瘤（RMS）的发病机制中的作用。我们的数据显示Notch途径基因在人RMS细胞系和患者样品中上调和活化。通过γ-分泌酶抑制剂（GSI）抑制Notch途径降低RMS细胞的体外增殖。通过RNAi敲低RBPJ表达抑制RMS细胞的锚定非依赖性生长和体内异种移植物的生长。此外，RBPJ的过表达促进RMS细胞的锚定非依赖性生长。此外，我们发现RBPJ调节RMS异种移植肿瘤的细胞周期并降低增殖。我们的研究结果表明，RBPJ调节RMS的生长，抑制RBPJ可能是RMS患者的有效治疗方法。
The Notch pathway regulates a broad spectrum of cell fate decisions and differentiation processes during fetal and postnatal development. In addition, the Notch pathway plays an important role in controlling tumorigenesis. However, the role of RBPJ, a transcription factor in the Notch pathway, in the development of tumors is largely unknown. In this study, we focused on the role of RBPJ in the pathogenesis of rhabdomyosarcoma (RMS). Our data showed that Notch pathway genes were upregulated and activated in human RMS cell lines and patient samples. Inhibition of the Notch pathway by a γ-secretase inhibitor (GSI) decreased the in vitro proliferation of RMS cells. Knockdown of RBPJ expression by RNAi inhibited the anchorage-independent growth of RMS cells and the growth of xenografts in vivo. Additionally, overexpression of RBPJ promoted the anchorage-independent growth of RMS cells. Further, we revealed that RBPJ regulated the cell cycle in RMS xenograft tumors and decreased proliferation. Our findings suggest that RBPJ regulates the RMS growth, and that the inhibition of RBPJ may be an effective therapeutic approach for patients with RMS.
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化疗对骨肉瘤细胞侵袭的抑制是由尿激酶纤溶酶原激活剂活性通过上调 EGR1 介导的。
影响因子：
3.7
作者：
Matsunoshita Y;Ijiri K;Ishidou Y;Nagano S;Yamamoto T;Nagao H;Komiya S;Setoguchi T
通讯作者：
Setoguchi T
影响因子：
2.2
作者：
Perez, Eduardo A.;Kassira, Noor;Sola, Juan E.
通讯作者：
Sola, Juan E.
DOI：
10.1158/1078-0432.ccr-08-2004
发表时间：
2009-04-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Mullendore ME;Koorstra JB;Li YM;Offerhaus GJ;Fan X;Henderson CM;Matsui W;Eberhart CG;Maitra A;Feldmann G
通讯作者：
Feldmann G
影响因子：
7.3
作者：
Aster, Jon C.;Blacklow, Stephen C.;Pear, Warren S.
通讯作者：
Pear, Warren S.
DOI：
10.1158/1078-0432.ccr-09-2823
发表时间：
2010-06-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Pannuti A;Foreman K;Rizzo P;Osipo C;Golde T;Osborne B;Miele L
通讯作者：
Miele L