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Nature:首秀!全新的肿瘤抑制蛋白,可阻止癌细胞在肝脏组织中扩散

2018-03-25 佚名 生物探索

3月21日,发表在《Nature》期刊上的一篇最新研究揭示了一种全新的肿瘤抑制蛋白——LHPP,可以阻止癌细胞在肝脏组织中的扩散。当缺失这一关键蛋白后,癌细胞生长将不受控制。科学家们认为,LHPP可以作为肝癌诊断、预后的重要标志物。

这种全新的肿瘤抑制蛋白“LHPP”是一种组氨酸磷酸酶(histidine phosphatase),由巴塞尔大学生物研究中心的Michael N. Hall教授带领团队发现。他们希望,以LHPP蛋白为标志物可以改善肝癌的诊疗,特别是肝细胞癌(HCC)。

肝癌是最常见的癌症类型之一,其中HCC是一种高死亡率的原发性肝癌,占原发性肝癌的90%。因为从肝炎发展至肝细胞癌的过程进展缓慢,无明显临床症状,所以患者确诊时往往已经进入晚期。此时肝脏受损严重,预后效果较差。而这一研究有望改变现状。

小鼠试验

Michael N. Hall团队的研究过程很有意思:他们以患有肝细胞癌的小鼠为模型(mTOR信号被特异性激活),并以健康小鼠为对照,在健康、肿瘤组织中对比分析了超4000种蛋白。最终,抑癌蛋白LHPP“脱颖而出”——LHPP存在于健康组织中,而且肿瘤组织中几乎没有。

进一步研究发现,这一全新蛋白可以有效抑制肿瘤的形成,维持肝功能。当缺乏LHPP时,肿瘤生长会不受控制,从而降低患者存活的几率。

癌症患者同样缺乏LHPP

肝癌起源于因突变而无限生长的细胞,通常肿瘤抑制因子可以阻止这些不受控制的细胞。遗憾的是,癌细胞的抗肿瘤蛋白基本都有缺陷。

“与小鼠模型相似,我们发现,肝癌患者体内的LHPP水平也显着下降。”文章一作Sravanth Hindupur解释道。而且,他们发现,疾病的严重程度、患者的预期寿命也与LHPP水平有关。因为完全缺乏这一肿瘤抑制因子的作用,癌症患者的平均生存期会缩短2年。

LHPP的抑癌机理

LHPP是一种磷酸酶,负责去除蛋白质上与组氨酸相连的磷酸基团。一旦缺乏LHPP,蛋白组氨酸磷酸化水平上调,导致细胞增殖不受控制,刺激肿瘤生长、扩散。

总之,LHPP是一种全新的肿瘤抑制因子,一旦缺失,组氨酸磷酸化会失控,从而促进肿瘤的发生和发展,最终影响患者的寿命。

原始出处:

Sravanth K. Hindupur et al, The protein histidine phosphatase LHPP is a tumour suppressor, Nature (2018). DOI: 10.1038/nature26140.

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    2018-05-25 liye789132251
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    2018-03-27 yxch36
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    2018-03-26 安好可好

    ICC研究的还是比较少

    0

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    2018-03-26 1221ee5fm23暂无昵称

    涨知识了!

    0

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