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Structural centrosome aberrations favor proliferation by abrogating microtubule-dependent tissue integrity of breast epithelial mammospheres

Schnerch, Dominik and Nigg, Erich A.. (2016) Structural centrosome aberrations favor proliferation by abrogating microtubule-dependent tissue integrity of breast epithelial mammospheres. Oncogene, 35 (21). pp. 2711-2722.

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Official URL: http://edoc.unibas.ch/43094/

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Abstract

Structural centrosome aberrations are frequently observed in early stage carcinomas, but their role in malignant transformation is poorly understood. Here, we examined the impact of overexpression of Ninein-like protein (Nlp) on the architecture of polarized epithelia in three-dimensional mammospheres. When Nlp was overexpressed to levels resembling those seen in human tumors, it formed striking centrosome-related bodies (CRBs), which sequestered Ninein and affected the kinetics of microtubule (MT) nucleation and release. In turn, the profound reorganization of the MT cytoskeleton resulted in mislocalization of several adhesion and junction proteins as well as the tumor suppressor Scribble, resulting in the disruption of epithelial polarity, cell-cell interactions and mammosphere architecture. Remarkably, cells harboring Nlp-CRBs displayed an enhanced proliferative response to epidermal growth factor. These results demonstrate that structural centrosome aberrations cause not only the disruption of epithelial polarity but also favor overproliferation, two phenotypes typically associated with human carcinomas.Oncogene advance online publication, 14 September 2015; doi:10.1038/onc.2015.332.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Cell Biology (Nigg)
UniBasel Contributors:Nigg, Erich A. and Schnerch, Dominik
Item Type:Article, refereed
Publisher:Macmillan
ISSN:0950-9232
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:01 Dec 2016 09:08
Deposited On:01 Dec 2016 09:08

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