Methionine restriction breaks obligatory coupling of cell proliferation and death by an oncogene Src in Drosophila.
Methionine restriction breaks obligatory coupling of cell proliferation and death by an oncogene Src in Drosophila.
复制标题
在果蝇中，甲基化酶的限制性酶切作用打破了癌基因Src对细胞增殖和死亡的强制性偶联。
作者：
Nishida H;Okada M;Yang L;Takano T;Tabata S;Soga T;Ho DM;Chung J;Minami Y;Yoo SK
癌基因通常促进细胞死亡以及增殖。癌基因如何驱动这些截然相反的现象仍有待解决。一个关键的问题是细胞死亡是否作为对异常增殖信号的反应或通过增殖独立机制发生。在这里，我们揭示了Src，第一个确定的癌基因，同时驱动细胞增殖和死亡的强制性耦合方式通过平行的MAPK途径。这两条MAPK通路从一个关键蛋白Slpr分叉。MAPK p38驱动增殖，而另一种MAPK JNK独立于增殖信号驱动凋亡。Src-p38诱导的增殖受甲硫氨酸介导的Tor信号转导调节。减少饮食中的甲硫氨酸可解除细胞增殖和死亡的强制性偶联，抑制肿瘤发生和肿瘤诱导的致死性。我们的研究结果提供了一个深入了解细胞如何进化到具有故障安全机制，阻止癌基因Src的肿瘤发生。我们还提出了一种基于饮食的方法，通过利用故障安全机制来规避肿瘤发生。
Oncogenes often promote cell death as well as proliferation. How oncogenes drive these diametrically opposed phenomena remains to be solved. A key question is whether cell death occurs as a response to aberrant proliferation signals or through a proliferation-independent mechanism. Here, we reveal that Src, the first identified oncogene, simultaneously drives cell proliferation and death in an obligatorily coupled manner through parallel MAPK pathways. The two MAPK pathways diverge from a lynchpin protein Slpr. A MAPK p38 drives proliferation whereas another MAPK JNK drives apoptosis independently of proliferation signals. Src-p38-induced proliferation is regulated by methionine-mediated Tor signaling. Reduction of dietary methionine uncouples the obligatory coupling of cell proliferation and death, suppressing tumorigenesis and tumor-induced lethality. Our findings provide an insight into how cells evolved to have a fail-safe mechanism that thwarts tumorigenesis by the oncogene Src. We also exemplify a diet-based approach to circumvent oncogenesis by exploiting the fail-safe mechanism.