Similarity in gene-regulatory networks suggests that cancer cells share characteristics of embryonic neural cells
Similarity in gene-regulatory networks suggests that cancer cells share characteristics of embryonic neural cells
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基因调控网络的相似性表明癌细胞具有胚胎神经细胞的特征
DOI：
10.1074/jbc.m117.785865
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发表时间：
2017-06
影响因子：
4.8
通讯作者：
Ying Cao
中科院分区：
文献类型：
--
作者：
Zan Zhang;Anhua Lei;Liyang Xu;Lu chen;Yonglong Chen;Xuena Zhang;Yan Gao;Xiaoli Yang;Min zhang;Ying Cao
癌细胞是由基因错误调节导致的细胞重编程产生的未成熟细胞，并且再分化有望减少恶性肿瘤。然而，目前尚不清楚癌细胞是否可以进行终末分化。在这里，我们发现，抑制zeste同源物2（EZH2）、组蛋白脱乙酰酶1和3（HDAC1和-3）、赖氨酸脱甲基酶1A（LSD1）或DNA甲基转移酶1（DNMT1）的表观遗传修饰酶增强子（这些酶都促进癌症的发生和进展）会导致有丝分裂后神经元样分化，并在不同的实体癌细胞系中丧失恶性特征。这些酶在神经元分化中的调节作用在于它们在胚胎神经前体/祖细胞中的内在活性。我们进一步发现，泛癌促基因的主要部分和泛癌促信号通路的信号转导子，包括上皮间质转化（EMT）间充质标志基因，在胚胎神经形成过程中表现出神经特异性表达。相比之下，许多肿瘤抑制基因，包括编码钙粘蛋白1（CDH1）的EMT上皮标记基因，表现出非神经表达或无表达。这种相关性表明癌细胞和胚胎神经细胞共享一个调节网络，介导肿瘤发生和神经发育。这种调节机制的相似性表明癌细胞可能具有胚胎神经细胞的特征。
Cancer cells are immature cells resulting from cellular reprogramming by gene misregulation, and redifferentiation is expected to reduce malignancy. It is unclear, however, whether cancer cells can undergo terminal differentiation. Here, we show that inhibition of the epigenetic modification enzyme enhancer of zeste homolog 2 (EZH2), histone deacetylases 1 and 3 (HDAC1 and -3), lysine demethylase 1A (LSD1), or DNA methyltransferase 1 (DNMT1), which all promote cancer development and progression, leads to postmitotic neuron-like differentiation with loss of malignant features in distinct solid cancer cell lines. The regulatory effect of these enzymes in neuronal differentiation resided in their intrinsic activity in embryonic neural precursor/progenitor cells. We further found that a major part of pan-cancer-promoting genes and the signal transducers of the pan-cancer-promoting signaling pathways, including the epithelial-to-mesenchymal transition (EMT) mesenchymal marker genes, display neural specific expression during embryonic neurulation. In contrast, many tumor suppressor genes, including the EMT epithelial marker gene that encodes cadherin 1 (CDH1), exhibited non-neural or no expression. This correlation indicated that cancer cells and embryonic neural cells share a regulatory network, mediating both tumorigenesis and neural development. This observed similarity in regulatory mechanisms suggests that cancer cells might share characteristics of embryonic neural cells.
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癌症干细胞产生的神经元支持癌症进展
影响因子：
39.3
作者：
Lu R;Fan C;Shangguan W;Liu Y;Li Y;Shang Y;Yin D;Zhang S;Huang Q;Li X;Meng W;Xu H;Zhou Z;Hu J;Li W;Liu L;Mo X
通讯作者：
Mo X
影响因子：
--
作者：
Moody SA;Je HS
通讯作者：
Je HS
DOI：
10.1002/9780470015902.a0026338
发表时间：
2017-01
期刊：
--
影响因子：
--
作者：
J. H. Kim;J. Bae;G. Kang
通讯作者：
J. H. Kim;J. Bae;G. Kang
影响因子：
2.6
作者：
P. Nieuwkoop;J. Faber
通讯作者：
P. Nieuwkoop;J. Faber
DOI：
10.1523/jneurosci.4037-15.2016
发表时间：
2016-02
期刊：
The Journal of Neuroscience
影响因子：
--
作者：
Ali Sharma;S. Klein;Luendreo P. Barboza;Niraj Lohdi;M. Toth
通讯作者：
Ali Sharma;S. Klein;Luendreo P. Barboza;Niraj Lohdi;M. Toth