Nature Metabolism:雄激素受体驱使的前列腺癌中,线粒体丙酮酸盐输入是代谢的一个弱点

2018-12-06 AlexYang MedSci原创

雄激素受体(AR)驱使的前列腺恶性肿瘤(PCa)的生长的特异性代谢基础仍旧大部分未知,当激素治疗失败的时候,阻碍了使用该疾病的代谢依赖性开发治疗策略途径的发展。最近,有研究人员指出,线粒体丙酮酸盐载体(MPC),一个关键的能够联系细胞质代谢和线粒体代谢的代谢途径关键因子,可以由AR进行转录水平上的调控。试验中对MPC的抑制能够限制细胞增殖和三羧酸循环(TCA)的代谢输出,包括了AR驱使PCa模型中

雄激素受体(AR)驱使的前列腺恶性肿瘤(PCa)的生长的特异性代谢基础仍旧大部分未知,当激素治疗失败的时候,阻碍了使用该疾病的代谢依赖性开发治疗策略途径的发展。

最近,有研究人员指出,线粒体丙酮酸盐载体(MPC),一个关键的能够联系细胞质代谢和线粒体代谢的代谢途径关键因子,可以由AR进行转录水平上的调控。试验中对MPC的抑制能够限制细胞增殖和三羧酸循环(TCA)的代谢输出,包括了AR驱使PCa模型中的脂肪生成和氧化磷酸化。另外,由于MPC抑制导致的代谢干扰能够激活eIF2α/ATF4整合应激响应(ISR)。ISR信号能够阻止细胞循环进展,并且能够增强TCA中谷氨酰胺的同化作用,从而重新获得代谢稳态。另外,研究人员确定了体内试验中,利用同位素代谢通量分析表明了MPC功能在PCa肿瘤中是可以操作的。反过来,研究人员在预临床PCa模型中利用一种临床可行的小分子来靶向MPC,MSDC0160,发现MPC的抑制能够抑制激素响应和趋势难治性条件下的肿瘤生长。

最后,研究人员指出,他们的发现鉴定了在AR驱使的前列腺肿瘤中,MPC可以作为一个可以操纵的治疗靶标。

原始出处:

David A. Bader, Sean M. Hartig, Vasanta Putluri et al. Mitochondrial pyruvate import is a metabolic vulnerability in androgen receptor-driven prostate cancer. Nature Metabolism. 19 Nov 2018.

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    2019-04-05 guojianrong
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    2019-01-05 liye789132251
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    2019-09-20 一闲
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    2018-12-11 kafei

    学习了谢谢

    0

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    2018-12-08 闆锋旦
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    2018-12-06 一个字-牛

    学习了谢谢分享

    0

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“近年来统计数据显示,我国前列腺癌患者5年生存率仅为53.5%,而美国前列腺癌患者的5年生存率达到了99%。”12月4日上午,在第八届上海泌尿肿瘤国际论坛召开前夕,中国抗癌协会泌尿男生殖系肿瘤专业委员会候任主委、复旦大学附属肿瘤医院副院长叶定伟教授在接受澎湃新闻(www.thepaper.cn)记者采访时透露了这一消息。叶定伟表示,中国目前没有明确前列腺癌的筛查标准,老百姓筛查意识不够强烈,这导致