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首页> 外文期刊>AIMS Genetics >MYC function and regulation in flies: how Drosophila has enlightened MYC cancer biology
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MYC function and regulation in flies: how Drosophila has enlightened MYC cancer biology

机译：果蝇中MYC的功能和调控：果蝇如何启发MYC癌症生物学

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Progress in our understanding of the complex signaling events driving human cancer would have been unimaginably slow without discoveries from Drosophila genetic studies. Significantly, many of the signaling pathways now synonymous with cancer biology were first identified as a result of elegant screens for genes fundamental to metazoan development. Indeed the name given to many core cancer-signaling cascades tells of their history as developmental patterning regulators in flies—e.g. Wingless (Wnt), Notch and Hippo. Moreover, astonishing insight has been gained into these complex signaling networks, and many other classic oncogenic signaling networks (e.g. EGFR/RAS/RAF/ERK, InR/PI3K/AKT/TOR), using sophisticated fly genetics. Of course if we are to understand how these signaling pathways drive cancer, we must determine the downstream program(s) of gene expression activated to promote the cell and tissue over growth fundamental to cancer. Here we discuss one commonality between each of these pathways: they are all implicated as upstream activators of the highly conserved MYC oncogene and transcription factor. MYC can drive all aspects of cell growth and cell cycle progression during animal development. MYC is estimated to be dysregulated in over 50% of all cancers, underscoring the importance of elucidating the signals activating MYC. We also discuss the FUBP1/FIR/FUSE system, which acts as a ‘cruise control’ on the MYC promoter to control RNA Polymerase II pausing and, therefore, MYC transcription in response to the developmental signaling environment. Importantly, the striking conservation between humans and flies within these major axes of MYC regulation has made Drosophila an extremely valuable model organism for cancer research. We therefore discuss how Drosophila studies have helped determine the validity of signaling pathways regulating MYC in vivo using sophisticated genetics, and continue to provide novel insight into cancer biology.
机译：如果没有果蝇遗传研究的发现，我们对驱动人类癌症的复杂信号事件的理解的进展将是不可想象的缓慢。重要的是，由于对后生动物发育基础的基因进行了优雅的筛选，首次鉴定了许多现在与癌症生物学同义的信号通路。确实，许多核心的癌症信号转导级联的名称都说明了它们作为果蝇中的发育模式调节剂的历史，例如Wingless（Wnt），Notch和Hippo。此外，使用复杂的蝇遗传学，已经对这些复杂的信号网络和许多其他经典的致癌信号网络（例如EGFR / RAS / RAF / ERK，InR / PI3K / AKT / TOR）获得了惊人的见识。当然，如果我们要了解这些信号通路如何驱动癌症，就必须确定激活的下游基因表达程序，以促进细胞和组织过度生长，这是癌症的根本。在这里，我们讨论了每种途径之间的共同点：它们都被认为是高度保守的MYC癌基因和转录因子的上游激活剂。 MYC可以驱动动物发育过程中细胞生长和细胞周期进程的各个方面。据估计，在所有癌症的50％以上中，MYC失调，强调了阐明激活MYC的信号的重要性。我们还将讨论FUBP1 / FIR / FUSE系统，该系统对MYC启动子起“巡航控制”作用，以控制RNA聚合酶II暂停，从而响应于发育信号环境，MYC转录。重要的是，在MYC调节的这些主要轴内，人与果蝇之间惊人的保守性使果蝇成为癌症研究中极为有价值的模型生物。因此，我们讨论果蝇研究如何使用复杂的遗传方法帮助确定体内调节MYC的信号传导途径的有效性，并继续为癌症生物学提供新的见解。

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