Centrosomes are the major microtubule organizing center of animal cells. Centrosomes contribute to timely bipolar spindle assembly during mitosis and participate in the regulation of other processes such as polarity establishment and cell migration. Centrosome numbers are tightly controlled during the cell cycle to ensure that mitosis is initiated with only two centrosomes. Deviations in centrosome number or structure are known to impact cell or tissue homeostasis and can impact different processes as diverse as proliferation, death or disease. Interestingly, defects in centrosome number seem to culminate with common responses, which depend on p53 activation even in different contexts such as development or cancer. p53 is a tumor suppressor gene with essential roles in the maintenance of genetic stability normally stimulated by various cellular stresses. Here, we review current knowledge and discuss how defects in centrosome structure and number can lead to different human pathologies.
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http://dx.doi.org/10.1016/j.sbi.2020.09.011 | DOI Listing |
Cell Death Dis
January 2025
Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors because of its high metastatic ability. The glutamine (Gln)-deficient microenvironment contributes to PDAC metastasis; however, the underlying molecular mechanisms remain unclear. Here, we demonstrated that melanophilin (MLPH) promotes PDAC metastasis by inducing the regrowth of primary cilia.
View Article and Find Full Text PDFCell Death Dis
January 2025
Mater Research Institute, The University of Queensland, Brisbane, QLD, Australia.
Polyploidy is a common outcome of chemotherapies, but there is conflicting evidence as to whether polyploidy is an adverse, benign or even favourable outcome. We show Aurora B kinase inhibitors efficiently promote polyploidy in many cell types, resulting in the cell cycle exit in RB and p53 functional cells, but hyper-polyploidy in cells with loss of RB and p53 function. These hyper-polyploid cells (>8n DNA content) are viable but have lost long-term proliferative potential in vitro and fail to form tumours in vivo.
View Article and Find Full Text PDFCurr Oncol
December 2024
Department of Tumor Pathology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan.
STIL is a regulatory protein essential for centriole biogenesis, and its dysregulation has been implicated in various diseases, including malignancies. However, its role in non-small-cell lung carcinoma (NSCLC) remains unclear. In this study, we examined STIL expression and its potential association with chromosomal numerical abnormalities (CNAs) in NSCLC using The Cancer Genome Atlas (TCGA) dataset, immunohistochemical analysis, and in vitro experiments with NSCLC cell lines designed to overexpress STIL.
View Article and Find Full Text PDFDev Cell
December 2024
Structural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany; Cell Biology and Biophysics Unit, EMBL, 69117 Heidelberg, Germany. Electronic address:
Centrosomes organize microtubules that are essential for mitotic divisions in animal cells. They consist of centrioles surrounded by pericentriolar material (PCM). Questions related to mechanisms of centriole assembly, PCM organization, and spindle microtubule formation remain unanswered, partly due to limited availability of molecular-resolution structural data inside cells.
View Article and Find Full Text PDFLeukemia
December 2024
Institute of Hematology and Center for Hemato-Oncological research (CREO), University of Perugia and Santa Maria della Misericordia Hospital, Perugia, Italy.
The nucleophosmin (NPM1) gene encodes for the most abundant nucleolar protein. Thanks to its property to act as histone chaperone and to shuttle between the nucleus and cytoplasm, the NPM1 protein is involved in multiple cellular function that are here extensively reviewed and include the formation of the nucleolus through liquid-liquid phase separation, regulation of ribosome biogenesis and transport, control of DNA repair and centrosome duplication as well as response to nucleolar stress. NPM1 is mutated in about 30-35% of adult acute myeloid leukemia (AML).
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