Nature2014-06-17 1:57 PM

多余的中心体怎样驱动侵袭性癌症 Oncogene-like induction of cellular invasion from centrosome amplification

论文摘要 

中心体是哺乳动物细胞中细胞周期的一个重要焦点,在控制和组织微管网络中起关键作用。有趣的是,癌细胞经常携带多种中心体,同时这篇论文也显示,多余的中心体能促进侵袭性癌细胞入侵,与由乳腺癌致癌基因ERBB2的过度表达所诱导的情形相似。另外,中心体放大还会在哺乳动物上皮细胞的三维培养中增强ERBB2 的效应,激活名为 “Rac1”的小GTPase。Rac1的激活已知在很多人类癌症中起重要作用。

Abstract 

Centrosome amplification has long been recognized as a feature of human tumours; however, its role in tumorigenesis remains unclear1. Centrosome amplification is poorly tolerated by non-transformed cells and, in the absence of selection, extra centrosomes are spontaneously lost2. Thus, the high frequency of centrosome amplification, particularly in more aggressive tumours3, raises the possibility that extra centrosomes could, in some contexts, confer advantageous characteristics that promote tumour progression. Using a three-dimensional model system and other approaches to culture human mammary epithelial cells, we find that centrosome amplification triggers cell invasion. This invasive behaviour is similar to that induced by overexpression of the breast cancer oncogene ERBB2 (ref. 4) and indeed enhances invasiveness triggered by ERBB2. Our data indicate that, through increased centrosomal microtubule nucleation, centrosome amplification increases Rac1 activity, which disrupts normal cell–cell adhesion and promotes invasion. These findings demonstrate that centrosome amplification, a structural alteration of the cytoskeleton, can promote features of malignant transformation.

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