Inactivation of MYC reverses tumorigenesis.
Inactivation of MYC reverses tumorigenesis.
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DOI：
10.1111/joim.12237
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发表时间：
2014-07
影响因子：
11.1
通讯作者：
Felsher DW
中科院分区：
文献类型：
--
作者：
Li Y;Casey SC;Felsher DW
MYC原癌基因是许多正常生物学程序的重要调节因子。当MYC作为一种致癌基因被激活时，它与大多数类型的人类癌症的发病机制有关。正常细胞中的MYC过表达通过多种遗传和表观遗传控制的检查点机制，包括增殖抑制、细胞凋亡和细胞衰老，抑制其致癌。当MYC在正确的表观遗传和遗传环境下被病理激活时，MYC绕过这些机制，驱动癌症的许多“标志性”特征，包括与DNA复制和转录、细胞增殖和生长、蛋白质合成和细胞代谢改变相关的不受控制的肿瘤生长。MYC还通过强制自我更新和废除细胞衰老和分化程序来决定肿瘤细胞的命运。此外，MYC影响肿瘤微环境，包括激活血管生成和抑制宿主免疫反应。刺激、短暂甚至部分抑制MYC回到其生理激活水平，可导致内在检查点机制的恢复，导致与肿瘤细胞增殖停滞、分化、衰老和凋亡相关的急性和持续的肿瘤消退，以及肿瘤微环境的重塑、免疫应答的募集和血管生成的关闭。因此，肿瘤似乎依赖于MYC癌基因，因为肿瘤细胞固有和宿主依赖的机制。MYC对于肿瘤发生的开始和维持的调节都是重要的。
The MYC proto-oncogene is an essential regulator of many normal biological programmes. MYC, when activated as an oncogene, has been implicated in the pathogenesis of most types of human cancers. MYC overexpression in normal cells is restrained from causing cancer through multiple genetically and epigenetically controlled checkpoint mechanisms, including proliferative arrest, apoptosis and cellular senescence. When pathologically activated in the correct epigenetic and genetic contexts, MYC bypasses these mechanisms and drives many of the ‘hallmark’ features of cancer, including uncontrolled tumour growth associated with DNA replication and transcription, cellular proliferation and growth, protein synthesis and altered cellular metabolism. MYC also dictates tumour cell fate by enforcing self-renewal and by abrogating cellular senescence and differentiation programmes. Moreover, MYC influences the tumour microenvironment, including activating angiogenesis and suppressing the host immune response. Provocatively, brief or even partial suppression of MYC back to its physiological levels of activation can lead to the restoration of intrinsic checkpoint mechanisms, resulting in acute and sustained tumour regression associated with tumour cells undergoing proliferative arrest, differentiation, senescence and apoptosis, as well as remodelling of the tumour microenvironment, recruitment of an immune response and shutdown of angiogenesis. Hence, tumours appear to be addicted to the MYC oncogene because of both tumour cell intrinsic and host-dependent mechanisms. MYC is important for the regulation of both the initiation and maintenance of tumorigenesis.
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影响因子：
11.2
作者：
Cao Z;Fan-Minogue H;Bellovin DI;Yevtodiyenko A;Arzeno J;Yang Q;Gambhir SS;Felsher DW
通讯作者：
Felsher DW
影响因子：
1.5
作者：
Calvisi, DF;Thorgeirsson, SS
通讯作者：
Thorgeirsson, SS
影响因子：
64.8
作者：
Dominguez-Sola, David;Ying, Carol Y.;Dalla-Favera, Riccardo
通讯作者：
Dalla-Favera, Riccardo
DOI：
10.1073/pnas.1107303108
发表时间：
2011-10-18
影响因子：
11.1
作者：
Choi, Peter S.;van Riggelen, Jan;Felsher, Dean W.
通讯作者：
Felsher, Dean W.
DOI：
10.1073/pnas.83.13.4834
发表时间：
1986-07-01
影响因子：
11.1
作者：
ESCOT, C;THEILLET, C;CALLAHAN, R
通讯作者：
CALLAHAN, R