Targeting NR4A1 (TR3) in cancer cells and tumors.
Targeting NR4A1 (TR3) in cancer cells and tumors.
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DOI：
10.1517/14728222.2011.547481
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发表时间：
2011-02
影响因子：
5.8
通讯作者：
Safe S
中科院分区：
文献类型：
--
作者：
Lee SO;Li X;Khan S;Safe S
NR 4A 1（TR 3，Nur 77）是转录因子核受体超家族的成员，有证据表明该受体在多种肿瘤类型中高度表达。此外，RNA干扰研究表明NR 4A 1在大多数癌症中表现出生长促进、血管生成和促生存活性。本文综述了几种细胞凋亡诱导剂激活NR 4A 1的核输出，随后形成线粒体NR 4A 1-bcl-2复合物，诱导细胞凋亡的内在途径的研究。还讨论了通过调节核NR 4A 1和核输出诱导癌细胞中NR 4A 1依赖性凋亡的细胞孢素B和相关化合物。详细讨论了一类较新的二吲哚甲烷类似物（C-DIM），包括1，1-双（3′-吲哚基）-1-（对甲氧基苯基）甲烷（DIM-C-pPhOCH 3）（NR 4A 1活化剂）和1，1-双（3′-吲哚基）-1-（对羟基苯基）甲烷（DIM-C-pPhOH）（NR 4A 1失活剂）。这些抗癌药物（C-DIM）严格通过核NR 4A 1起作用，并诱导癌细胞和肿瘤的凋亡。很明显，NR 4A 1在癌细胞和肿瘤中起着重要的促癌作用，并且越来越多的证据表明，这种受体可以被抗癌药物靶向，这些抗癌药物通过NR 4A 1依赖性和非依赖性途径诱导细胞死亡。此外，由于这些化合物中的许多表现出相对低的毒性，它们代表了一类重要的基于机制的抗癌药物，具有良好的临床应用潜力。
NR4A1 (TR3, Nur77) is a member of the nuclear receptor superfamily of transcription factors and there is evidence that this receptor is highly expressed in multiple tumor types. Moreover, RNA interference studies indicate that NR4A1 exhibits growth promoting, angiogenic and prosurvival activity in most cancers. This review summarizes studies on several apoptosis-inducing agents that activate nuclear export of NR4A1 which subsequently forms a mitochondrial NR4A1-bcl-2 complex that induces the intrinsic pathway for apoptosis. Cytosporone B and related compounds that induce NR4A1-dependent apoptosis in cancer cells through both modulation of nuclear NR4A1 and nuclear export are also discussed. A relatively new class of diindolylmethane analogs (C-DIMs) including 1,1-bis(3′-indolyl)-1-(p-methoxyphenyl)methane (DIM-C-pPhOCH3) (NR4A1 activator) and 1,1-bis(3′-indolyl)-1-(p-hydroxyphenyl)methane (DIM-C-pPhOH) (NR4A1 deactivator) are discussed in more detail. These anticancer drugs (C-DIMs) act strictly through nuclear NR4A1 and induce apoptosis in cancer cells and tumors. It is clear that NR4A1 plays an important pro-oncogenic role in cancer cells and tumors, and there is increasing evidence that this receptor can be targeted by anticancer drugs that induce cell death via NR4A1-dependent and -independent pathways. Moreover, since many of these compounds exhibit relatively low toxicity, they represent an important class of mechanism-based anticancer drugs with excellent potential for clinical applications.
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影响因子：
6.4
作者：
Chen, GQ;Lin, BZ;Zhang, XK
通讯作者：
Zhang, XK
影响因子：
11.2
作者：
Chadalapaka G;Jutooru I;Chintharlapalli S;Papineni S;Smith R 3rd;Li X;Safe S
通讯作者：
Safe S
DOI：
10.1073/pnas.88.21.9543
发表时间：
1991-11-01
影响因子：
11.1
作者：
BJELDANES, LF;KIM, JY;BRADFIELD, CA
通讯作者：
BRADFIELD, CA
影响因子：
13.5
作者：
Chen, Leilei;Hu, Liang;Guan, Xin-Yuan
通讯作者：
Guan, Xin-Yuan
影响因子：
64.5
作者：
Bookout, Angie L.;Jeong, Yangsik;Mangelsdorf, David J.
通讯作者：
Mangelsdorf, David J.