MYC Ran Up the Clock: The Complex Interplay between MYC and the Molecular Circadian Clock in Cancer.
MYC Ran Up the Clock: The Complex Interplay between MYC and the Molecular Circadian Clock in Cancer.
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DOI：
10.3390/ijms22147761
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发表时间：
2021-07-20
影响因子：
5.6
通讯作者：
Altman BJ
中科院分区：
文献类型：
--
作者：
Burchett JB;Knudsen-Clark AM;Altman BJ
已知MYC癌蛋白及其家族成员N-MYC和L-MYC驱动多种人类癌症。新出现的证据表明，MYC与癌症中的分子钟具有双向关系。在大多数真核细胞和生物体中，分子钟作为一种适应光/暗周期的机制，负责昼夜节律（~24小时）。人类昼夜节律的破坏，例如通过轮班工作，可能是癌症的一个风险因素，但与MYC等致癌驱动因素的联系以前并没有得到很好的理解。在这篇综述中，我们研究了最近的证据，表明癌细胞中的MYC可以破坏分子钟；相反，癌症中的分子钟破坏可以解除对MYC的调节并使其升高。由于MYC和分子钟控制着许多相同的过程，我们随后考虑MYC和分子钟在肿瘤生物学的几个选择方面的竞争，包括染色质状态、全局转录谱、代谢重连接和肿瘤中的免疫浸润。最后，我们讨论了如何在人类肿瘤中监测或诊断分子钟，以及MYC抑制如何潜在地恢复分子钟功能。对癌症中分子钟和MYC之间关系的进一步研究可能会揭示以前未被怀疑的脆弱性，这可能会导致新的治疗策略。
The MYC oncoprotein and its family members N-MYC and L-MYC are known to drive a wide variety of human cancers. Emerging evidence suggests that MYC has a bi-directional relationship with the molecular clock in cancer. The molecular clock is responsible for circadian (~24 h) rhythms in most eukaryotic cells and organisms, as a mechanism to adapt to light/dark cycles. Disruption of human circadian rhythms, such as through shift work, may serve as a risk factor for cancer, but connections with oncogenic drivers such as MYC were previously not well understood. In this review, we examine recent evidence that MYC in cancer cells can disrupt the molecular clock; and conversely, that molecular clock disruption in cancer can deregulate and elevate MYC. Since MYC and the molecular clock control many of the same processes, we then consider competition between MYC and the molecular clock in several select aspects of tumor biology, including chromatin state, global transcriptional profile, metabolic rewiring, and immune infiltrate in the tumor. Finally, we discuss how the molecular clock can be monitored or diagnosed in human tumors, and how MYC inhibition could potentially restore molecular clock function. Further study of the relationship between the molecular clock and MYC in cancer may reveal previously unsuspected vulnerabilities which could lead to new treatment strategies.
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DOI：
10.1073/pnas.1619320114
发表时间：
2017-05-16
影响因子：
11.1
作者：
Anafi, Ron C.;Francey, Lauren J.;Kim, Junhyong
通讯作者：
Kim, Junhyong
影响因子：
50.3
作者：
Carroll PA;Diolaiti D;McFerrin L;Gu H;Djukovic D;Du J;Cheng PF;Anderson S;Ulrich M;Hurley JB;Raftery D;Ayer DE;Eisenman RN
通讯作者：
Eisenman RN
DOI：
10.1126/science.aac9935
发表时间：
2016-04-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Casey SC;Tong L;Li Y;Do R;Walz S;Fitzgerald KN;Gouw AM;Baylot V;Gütgemann I;Eilers M;Felsher DW
通讯作者：
Felsher DW
影响因子：
5.5
作者：
Altman BJ
通讯作者：
Altman BJ
影响因子：
8.6
作者：
Boike L;Cioffi AG;Majewski FC;Co J;Henning NJ;Jones MD;Liu G;McKenna JM;Tallarico JA;Schirle M;Nomura DK
通讯作者：
Nomura DK