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Centrosome – a promising anti-cancer target

机译:中心体–有望成为抗癌靶标

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摘要

The centrosome, an organelle discovered >100 years ago, is the main microtubule-organizing center in mammalian organisms. The centrosome is composed of a pair of centrioles surrounded by the pericentriolar material (PMC) and plays a major role in the regulation of cell cycle transitions (G1-S, G2-M, and metaphase-anaphase), ensuring the normality of cell division. Hundreds of proteins found in the centrosome exert a variety of roles, including microtubule dynamics, nucleation, and kinetochore–microtubule attachments that allow correct chromosome alignment and segregation. Errors in these processes lead to structural (shape, size, number, position, and composition), functional (abnormal microtubule nucleation and disorganized spindles), and numerical (centrosome amplification [CA]) centrosome aberrations causing aneuploidy and genomic instability. Compelling data demonstrate that centrosomes are implicated in cancer, because there are important oncogenic and tumor suppressor proteins that are localized in this organelle and drive centrosome aberrations. Centrosome defects have been found in pre-neoplasias and tumors from breast, ovaries, prostate, head and neck, lung, liver, and bladder among many others. Several drugs/compounds against centrosomal proteins have shown promising results. Other drugs have higher toxicity with modest or no benefits, and there are more recently developed agents being tested in clinical trials. All of this emerging evidence suggests that targeting centrosome aberrations may be a future avenue for therapeutic intervention in cancer research.
机译:中心体是100多年前发现的细胞器,是哺乳动物有机体中的主要微管组织中心。中心体由一对中心体组成,周围被中心体周围物质(PMC)包围,在调节细胞周期转变(G1-S,G2-M和中期-后期)中起主要作用,从而确保细胞分裂的正常进行。在中心体中发现的数百种蛋白质起着各种作用,包括微管动力学,成核作用以及动粒-微管附着,它们可以使染色体正确对齐和分离。这些过程中的错误会导致结构(形状,大小,数量,位置和组成),功能(异常的微管成核和纺锤体混乱)以及数值(中心体扩增[CA])中心体畸变,从而导致非整倍性和基因组不稳定。有说服力的数据表明,中心体与癌症有关,因为重要的致癌蛋白和肿瘤抑制蛋白位于该细胞器中并驱动中心体畸变。在乳腺前病变和来自乳腺,卵巢,前列腺,头颈,肺,肝和膀胱等的肿瘤中发现了中心体缺陷。几种抗中心体蛋白的药物/化合物已显示出令人鼓舞的结果。其他药物具有较高的毒性,但有中等或无益处,并且有更多近来开发的药物正在临床试验中进行测试。所有这些新兴证据表明,靶向中心体畸变可能是癌症研究中治疗性干预的未来途径。

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