Centrosome amplification has severe consequences during development and is thought to contribute to a variety of diseases such as cancer and microcephaly. However, the adverse effects of centrosome amplification in epithelia are still not known. Here, we investigate the consequences of centrosome amplification in the Drosophila wing disc epithelium. We found that epithelial cells exhibit mechanisms of clustering but also inactivation of extra centrosomes. Importantly, these mechanisms are not fully efficient, and both aneuploidy and cell death can be detected. Epithelial cells with extra centrosomes generate tumors when transplanted into WT hosts and inhibition of cell death results in tissue over-growth and disorganization. Using SILAC-fly, we found that Moesin, a FERM domain protein, is specifically upregulated in wing discs with extra centrosomes. Moesin localizes to the centrosomes and mitotic spindle during mitosis, and we show that Moesin upregulation influences extra-centrosome behavior and robust bipolar spindle formation. This study provides a mechanistic explanation for the increased aneuploidy and transformation potential primed by centrosome amplification in epithelial tissues.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4386030 | PMC |
http://dx.doi.org/10.1016/j.cub.2015.01.066 | DOI Listing |
Proc Natl Acad Sci U S A
December 2024
Department of Infectious Diseases and Pathobiology, Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland.
Taxanes are frequently used anticancer drugs known to kill tumor cells by inducing mitotic aberrations and segregation defects. A defining feature of specific cancers, notably triple-negative breast cancer (TNBC) and particularly those deficient in BRCA1, is chromosomal instability (CIN). Here, we focused on understanding the mechanisms of docetaxel-induced cytotoxicity, especially in the context of BRCA1-deficient TNBC.
View Article and Find Full Text PDFCancer Metastasis Rev
November 2024
Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Centrosomes serve as microtubule-organizing organelles that function in spindle pole organization, cell cycle progression, and cilia formation. A non-canonical role of centrosomes that has gained traction in recent years is the ability to act as signal transduction centers. Centrosome amplification, which includes numerical and structural aberrations of centrosomes, is a candidate hallmark of cancer.
View Article and Find Full Text PDFSci Adv
November 2024
Armenise-Harvard Laboratory of Cell Division, Department of Cellular, Computational and Integrative Biology-CIBIO, University of Trento, Trento, Italy.
Centrosomes are membrane-less organelles that orchestrate a wide array of biological functions by acting as microtubule organizing centers. Here, we report that caspase-2-driven apoptosis is elicited in blood cells failing cytokinesis and that extra centrosomes are necessary to trigger this cell death. Activation of caspase-2 depends on the PIDDosome multi-protein complex, and priming of PIDD1 at extra centrosomes is necessary for pathway activation.
View Article and Find Full Text PDFNat Commun
October 2024
Institute for Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.
Centrioles define centrosome structure and function. Deregulation of centriole numbers can cause developmental defects and cancer. The p53 tumor suppressor limits the growth of cells lacking or harboring additional centrosomes and can be engaged by the "mitotic surveillance" or the "PIDDosome pathway", respectively.
View Article and Find Full Text PDFEMBO Rep
October 2024
Institute for Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!