MYC, Cell Competition, and Cell Death in Cancer: The Inseparable Triad.
MYC, Cell Competition, and Cell Death in Cancer: The Inseparable Triad.
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DOI：
10.3390/genes8040120
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发表时间：
2017-04-17
期刊：
影响因子：
3.5
通讯作者：
Grifoni D
中科院分区：
文献类型：
--
作者：
Di Giacomo S;Sollazzo M;Paglia S;Grifoni D
MYC家族蛋白在癌症中的失调与基因表达的全局重编程相关，最终促进糖酵解途径、细胞生长和增殖。众所周知，MYC上调触发正常组织中的细胞自主凋亡，而坦率地说，恶性细胞对凋亡刺激产生抗性，部分原因是MYC成瘾。除了诱导细胞自主凋亡外，MYC上调还能够通过称为“细胞竞争”的进化保守机制触发非细胞自主凋亡死亡。关于MYC和细胞死亡之间的这种亲密和双重关系，最近在果蝇癌症模型中获得的证据表明，在早期肿瘤发生中，MYC上调指导突变细胞的克隆扩增，而周围组织经历非细胞自主死亡。在这种情况下，细胞凋亡抑制被证明可以抑制肿瘤生长并恢复野生型表型。这表明依赖于MYC上调的细胞自主和非细胞自主凋亡可能以不同的方式塑造肿瘤生长，因此需要根据这种新的复杂性水平重新考虑细胞死亡在癌症中的作用。在这里，我们回顾了最近的文献MYC和细胞竞争中获得的果蝇，特别强调细胞死亡的相关性，细胞竞争，更普遍的是，癌症。这些研究结果的哺乳动物癌症的理解可能产生的影响进行了讨论。
Deregulation of MYC family proteins in cancer is associated with a global reprogramming of gene expression, ultimately promoting glycolytic pathways, cell growth, and proliferation. It is well known that MYC upregulation triggers cell-autonomous apoptosis in normal tissues, while frankly malignant cells develop resistance to apoptotic stimuli, partly resulting from MYC addiction. As well as inducing cell-autonomous apoptosis, MYC upregulation is able to trigger non cell-autonomous apoptotic death through an evolutionarily conserved mechanism known as “cell competition”. With regard to this intimate and dual relationship between MYC and cell death, recent evidence obtained in Drosophila models of cancer has revealed that, in early tumourigenesis, MYC upregulation guides the clonal expansion of mutant cells, while the surrounding tissue undergoes non-cell autonomous death. Apoptosis inhibition in this context was shown to restrain tumour growth and to restore a wild-type phenotype. This suggests that cell-autonomous and non cell-autonomous apoptosis dependent on MYC upregulation may shape tumour growth in different ways, soliciting the need to reconsider the role of cell death in cancer in the light of this new level of complexity. Here we review recent literature about MYC and cell competition obtained in Drosophila, with a particular emphasis on the relevance of cell death to cell competition and, more generally, to cancer. Possible implications of these findings for the understanding of mammalian cancers are also discussed.