Oncogene-like induction of cellular invasion from centrosome amplification View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-06

AUTHORS

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

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. More... »

PAGES

167

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nature13277

DOI

http://dx.doi.org/10.1038/nature13277

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1022541737

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24739973


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