Oncogene-like induction of cellular invasion from centrosome amplification

Susana A. Godinho, Remigio Picone, Mithila Burute, Regina Dagher, Ying Su, Cheuk T. Leung, Kornelia Polyak, Joan S. Brugge, Manuel Théry, David Pellman

Research output: Contribution to journalArticle

191 Scopus citations

Abstract

Centrosome amplification has long been recognized as a feature of human tumours; however, its role in tumorigenesis remains unclear. Centrosome amplification is poorly tolerated by non-transformed cells and, in the absence of selection, extra centrosomes are spontaneously lost. Thus, the high frequency of centrosome amplification, particularly in more aggressive tumours, 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.

Original languageEnglish (US)
Pages (from-to)167-171
Number of pages5
JournalNature
Volume510
Issue number7503
DOIs
StatePublished - Jan 1 2014

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    Godinho, S. A., Picone, R., Burute, M., Dagher, R., Su, Y., Leung, C. T., Polyak, K., Brugge, J. S., Théry, M., & Pellman, D. (2014). Oncogene-like induction of cellular invasion from centrosome amplification. Nature, 510(7503), 167-171. https://doi.org/10.1038/nature13277