Exposure to toxic and carcinogenic metals is widespread; however, their mechanisms of action remain largely unknown. One potential mechanism for metal-induced carcinogenicity and toxicity is centrosome amplification. Here we review the mechanisms for metal-induced centrosome amplification, including arsenic, chromium, mercury and nano-titanium dioxide.
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http://dx.doi.org/10.1042/BST0381687 | DOI Listing |
Development
January 2025
Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Karyotype instability in the germline leads to infertility. Unlike the female germline, the male germline continuously produces fertile sperm throughout life. Here we present a molecular network responsible for maintaining karyotype stability in the male mouse germline.
View Article and Find Full Text PDFEur J Med Chem
January 2025
Department of Respiratory and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, Institute of Respiratory Healthand, Department of Frontiers Science Center for Disease-related Molecular Network, Core Facilities, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. Electronic address:
NEK2, a serine/threonine protein kinase, is integral to mitotic events such as centrosome duplication and separation, microtubule stabilization, spindle assembly checkpoint, and kinetochore attachment. However, NEK2 overexpression leads to centrosome amplification and chromosomal instability, which are significantly associated with various malignancies, including liver, breast, and non-small cell lung cancer. This overexpression could facilitate tumor development and confer resistance to therapy by promoting aberrant cell division and centrosome amplification.
View Article and Find Full Text PDFJ Biol Chem
January 2025
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio, USA. Electronic address:
Selective inhibitors that target cyclin dependent kinases 4 and 6 (CDK4/6i) are FDA approved for treatment of a subset of breast cancers and are being evaluated in numerous clinical trials for other cancers. Despite this advance, a subset of tumors are intrinsically resistant to these drugs and acquired resistance is nearly inevitable. Recent mechanistic evidence suggests that in addition to stalling the cell cycle, the anti-tumor effects of CDK4/6i involve the induction of chromosomal instability (CIN).
View Article and Find Full Text PDFEMBO Rep
January 2025
Cellular and Molecular Physiology, Institute of Systems Molecular and Integrative Biology, University of Liverpool, Crown St, Liverpool, L69 3BX, UK.
Cancer cells often display centrosome amplification, requiring the kinesin KIFC1/HSET for centrosome clustering to prevent multipolar spindles and cell death. In parallel siRNA screens of deubiquitinase enzymes, we identify OTUD6B as a positive regulator of KIFC1 expression that is required for centrosome clustering in triple-negative breast cancer (TNBC) cells. OTUD6B can localise to centrosomes and the mitotic spindle and interacts with KIFC1.
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.
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