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• W2036747263 abstract "Cancer cells often have extra centrosomes, a paradox considering the detrimental effect extra centrosomes usually have on cell division; a study of human cells reveals that extra centrosomes can promote cancer cell invasion phenotypes through a pathway involving increased microtubule nucleation and Rac1 activity. The centrosome is an important focus of the cell cycle in mammalian cells, with a crucial role in controlling the organization of the microtubule network. Intriguingly, cancer cells often carry multiple centrosomes, and this paper demonstrates that the extra centrosomes can promote aggressive cancer cell invasion resembling that induced by overexpression of the breast cancer oncogene ERBB2. In addition, centrosome amplification augments the effects of ERBB2 in three-dimensional cultures of mammary epithelial cells and activates the small GTPase Rac1. Rac1 activation is known to play a major role in many human cancers. 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." @default.
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• W2036747263 date "2014-04-13" @default.
• W2036747263 modified "2023-10-17" @default.
• W2036747263 title "Oncogene-like induction of cellular invasion from centrosome amplification" @default.
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• W2036747263 doi "https://doi.org/10.1038/nature13277" @default.
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