Genome instability (GI) and centrosomal alterations are common traits in human cancer [1, 2]. It is suspected that centrosome dysfunction may cause tumors by bringing about GI, but direct experimental proof is still lacking [3]. To explore the possible functional link between centrosome function and overgrowth, we have assayed the tumorigenic potential of a series of mutants that affect different centrosomal proteins in Drosophila. We have found that a significant number of such mutant conditions are tumorigenic in larval brain tissue, where self-renewing asymmetric division of neural stem cells is frequent, but not in symmetrically dividing epithelial cells. We have also found that mutations that increase GI without causing centrosome dysfunction are not tumorigenic in our assay. From these observations, we conclude that the tumors caused by centrosome dysfunction cannot be explained solely by the resulting genome instability. We propose that such tumors might be caused by impaired asymmetric division of neural stem cells [4]. These results show that centrosome loss, far from being innocuous, is a potentially dangerous condition in flies.
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http://dx.doi.org/10.1016/j.cub.2008.07.029 | DOI Listing |
Comput Biol Chem
December 2024
Department of Urology, Qilu Hospital of Shandong University Dezhou Hospital, Dezhou 253000, China. Electronic address:
Background: Centrosome amplification (CA) has been shown to be capable of initiating tumorigenesis with metastatic potential and enhancing cell invasion. We were interested in discovering how centrosome amplification-associated signature affects the prediction of prognosis and response to therapy in kidney renal clear cell carcinoma (KIRC).
Methods And Materials: The TCGA-KIRC dataset was used to construct a centrosome amplification-associated signature using the random survival forest analysis and Cox regression analysis, and the ICGC and GEO datasets were employed for signature validation.
Sci Adv
December 2024
Laboratory of Cell Cycle Regulation, Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad 500039, India.
Dysfunction of the centrosome, the major microtubule-organizing center of the cell, is implicated in microcephaly. Haploinsufficiency of mixed-lineage leukemia (MLL/KMT2A) protein causes Wiedemann-Steiner syndrome (WSS), a neurodevelopmental disorder associated with microcephaly. However, whether MLL has a function at the centrosome is not clear.
View Article and Find Full Text PDFBiochem Biophys Res Commun
December 2024
Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA; Graduate Program in Genetics and Epigenetics, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA. Electronic address:
The primary cilium is a cellular antenna to orchestrate cell growth and differentiation. Deficient or dysfunctional cilia are frequently linked to skeletal abnormalities. Previous research demonstrated that ciliary proteins regulating axoneme elongation are essential for skeletogenesis.
View Article and Find Full Text PDFJ Cell Biol
December 2024
Institut du Fer à Moulin , Paris, France.
Subcortical heterotopia is a cortical malformation associated with epilepsy, intellectual disability, and an excessive number of cortical neurons in the white matter. Echinoderm microtubule-associated protein like 1 (EML1) mutations lead to subcortical heterotopia, associated with abnormal radial glia positioning in the cortical wall, prior to malformation onset. This perturbed distribution of proliferative cells is likely to be a critical event for heterotopia formation; however, the underlying mechanisms remain unexplained.
View Article and Find Full Text PDFDev Biol
January 2025
Institute of Evolution & Marine Biodiversity, Ocean University of China, Qingdao, 266003, China; Key Laboratory of Evolution and Marine Biodiversity of the Ministry of Education, Institute of Evolution and Marine Biodiversity, Ocean University of China, Qingdao, 266003, China. Electronic address:
PLK4 plays a crucial role in centriole duplication, which is essential for maintaining cellular processes such as cell division, cytoskeletal stability, and cilia formation. However, the mechanisms of PLK4 remain incompletely understood, especially in the embryonic development of vertebrate species. In this study, we observed that Plk4 dysfunction led to abnormal embryonic development in zebrafish, characterized by symptoms such as dark and wrinkled skin, microphthalmia, and body axis curvature.
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