Transcription addiction: can we garner the Yin and Yang functions of E2F1 for cancer therapy?
Transcription addiction: can we garner the Yin and Yang functions of E2F1 for cancer therapy?
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DOI：
10.1038/cddis.2014.326
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发表时间：
2014-08-07
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
经典地，作为转录因子家族，已知E2 F调节各种基因的表达，所述基因的产物涉及多种生物学功能，其中许多在包括癌症的疾病中被解除调节。E2 F在大多数人类癌症中失调和过度活跃，在几乎所有癌症中具有背景依赖性，二分法和矛盾的作用。癌细胞对转录有着永不满足的需求，以确保基因产物可用于维持支持其快速生长和存活的各种生物过程。在这种情况下，切断支持转录依赖的转录因子的过度活跃可能是一种有价值的治疗策略。然而，靶向转录因子的最大挑战之一是对非癌细胞的全局影响，因为它们通常控制细胞功能。最近，人们越来越认识到靶向转录因子的致癌激活以调节转录成瘾而不影响细胞功能所需的正常活性的可能性。在这篇综述中，我们使用E2 F1作为原型转录因子来解决转录因子在癌细胞功能中的活性。考虑到E2 F1对UV（皮肤黑色素瘤的一种致病因素）的响应执行关键功能，并且位于CDKN 2A/pRb轴的下游，该轴在黑色素瘤中经常被解除调节，因此我们将重点放在黑色素瘤上。此外，黑色素瘤中E2 F1的激活也可以独立于CDKN 2A的丢失而发生。鉴于其激活状态和转录控制过多的基因参与调节黑色素瘤的发展和进展的能力，我们回顾了目前的文献中的差异作用，在控制信号通路参与黑色素瘤以及治疗耐药性，并讨论断奶黑色素瘤细胞从E2 F1介导的转录依赖黑色素瘤管理的实用价值。
Classically, as a transcription factor family, the E2Fs are known to regulate the expression of various genes whose products are involved in a multitude of biological functions, many of which are deregulated in diseases including cancers. E2F is deregulated and hyperactive in most human cancers with context dependent, dichotomous and contradictory roles in almost all cancers. Cancer cells have an insatiable demand for transcription to ensure that gene products are available to sustain various biological processes that support their rapid growth and survival. In this context, cutting-off hyperactivity of transcription factors that support transcription dependence could be a valuable therapeutic strategy. However, one of the greatest challenges of targeting a transcription factor is the global effects on non-cancerous cells given that they control cellular functions in general. Recently, there is growing realization regarding the possibility to target the oncogenic activation of transcription factors to modulate transcription addiction without affecting the normal activity required for cell functions. In this review, we used E2F1 as a prototype transcription factor to address transcription factor activity in cancer cell functions. We focused on melanoma considering that E2F1 executes critical functions in response to UV, an etiological factor of cutaneous melanoma and lies immediately downstream of the CDKN2A/pRb axis, which is frequently deregulated in melanoma. Further, activation of E2F1 in melanomas can also occur independent of loss of CDKN2A. Given its activated status and the ability to transcriptionally control a plethora of genes involved in regulating melanoma development and progression, we review the current literature on its differential role in controlling signaling pathways involved in melanoma as well as therapeutic resistance, and discuss the practical value of weaning melanoma cells from E2F1-mediated transcription dependence for melanoma management.
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影响因子：
8
作者：
Bell, L. A.;O'Prey, J.;Ryan, K. M.
通讯作者：
Ryan, K. M.
DOI：
10.4161/cc.21476
发表时间：
2012-08-15
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Alla V;Kowtharapu BS;Engelmann D;Emmrich S;Schmitz U;Steder M;Pützer BM
通讯作者：
Pützer BM
DOI：
10.1073/pnas.0600213103
发表时间：
2006-06-27
影响因子：
11.1
作者：
Chen, Kevin G.;Valencia, Julio C.;Gottesman, Michael M.
通讯作者：
Gottesman, Michael M.
影响因子：
4.6
作者：
Carcagno, Abel L.;Ogara, Maria F.;Canepa, Eduardo T.
通讯作者：
Canepa, Eduardo T.
影响因子：
8
作者：
Conner, EA;Lemmer, ER;Thorgeirsson, SS
通讯作者：
Thorgeirsson, SS