Nature Cancer:中科院尹慧勇团队发现醛固酮酶B通过代谢重编程抑制肝癌的发生

2020-07-13 MedSci原创 MedSci原创

最近,来自中国科学院上海营养与健康研究所的尹慧勇团队发现,肝脏醛糖酶B(Aldob)通过直接结合和抑制磷酸戊糖途径中的限速酶,葡萄糖-6-磷酸脱氢酶(G6PD),来抑制HCC。

代谢重编程是癌症的核心标志,但它在肝细胞癌发生(HCC)中的定义仍然很模糊。

最近,来自中国科学院上海营养与健康研究所的尹慧勇团队发现,肝脏醛糖酶B(Aldob)通过直接结合和抑制磷酸戊糖途径中的限速酶,葡萄糖-6-磷酸脱氢酶(G6PD),来抑制HCC。

人类肿瘤中Aldob的阶段性减少和G6PD的增加与HCC患者的不良预后相关。全局性或肝脏特异性Aldob敲除通过增强G6PD活性和磷酸戊糖途径代谢促进小鼠肿瘤发生,而药物抑制或基因敲除G6PD可抑制HCC。

一致地,在Aldob基因敲除小鼠中恢复Aldob的表达可减轻肿瘤的发生。

研究人员进一步证明,Aldob在Aldob-G6PD-p53复合物中增强了p53介导的G6PD的抑制作用。这种支架效应是独立于Aldob酶活性的。

因此,该研究揭示了HCC中由于Aldob丢失而导致的一种新的代谢重编程模式,这是HCC的潜在治疗策略。

 

原始出处:

Min Li et al. Aldolase B suppresses hepatocellular carcinogenesis by inhibiting G6PD and pentose phosphate pathways, Nature Cancer (2020). 

 

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    2020-11-25 gous
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    2021-03-27 liye789132251
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    2020-07-15 cmsvly
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    2020-07-13 留走人康

    肝癌,接下来就要细分了,对于体质好的病人,能否将PD-1类+抗血管新生+放疗等相结合,甚至有必要用TACE进行减负

    0

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