Search results for "centrosome"
showing 10 items of 36 documents
Centrioles Shape ERK Signaling Outcomes to Support Lung Branching
2021
Centrioles comprise the heart of centrosomes, where they organize microtubules. To study the function of centrioles in development, we genetically disrupted centrioles throughout the mouse endoderm. Surprisingly, removing centrioles from endoderm did not disrupt intestinal growth or development. In contrast, in the lung, loss of centrioles blocked branching. In lung, loss of centrioles led to apoptosis specifically of SOX2-expressing airway epithelial cells. Loss of centrioles also activated p53. Deleting p53 in mice with acentriolar endoderm rescued SOX2+ cell survival, lung branching and viability. To investigate why endoderm-wide p53 activation specifically disrupted SOX2+ cell survival,…
Centrosome amplification induced by hydroxyurea leads to aneuploidy in pRB deficient human and mouse fibroblasts.
2006
Alterations in the number and/or morphology of centrosomes are frequently observed in human tumours. However, it is still debated if a direct link between supernumerary centrosomes and tumorigenesis exists and if centrosome amplification could directly cause aneuploidy. Here, we report that hydroxyurea treatment induced centrosome amplification in both human fibroblasts expressing the HPV16 -E6-E7 oncoproteins, which act principally by targeting p53 and pRB, respectively, and in conditional pRB deficient mouse fibroblasts. Following hydroxyurea removal both normal and p53 deficient human fibroblasts arrested. On the contrary pRB deficient fibroblasts entered the cell cycle generating aneupl…
TOPORS, implicated in retinal degeneration, is a cilia-centrosomal protein.
2011
et al.
Differential expression and interaction with the visual G-protein transducin of centrin isoforms in mammalian photoreceptor cells.
2004
Photoisomerization of rhodopsin activates a heterotrimeric G-protein cascade leading to closure of cGMP-gated channels and hyperpolarization of photoreceptor cells. Massive translocation of the visual G-protein transducin, Gt, between subcellular compartments contributes to long term adaptation of photoreceptor cells. Ca(2+)-triggered assembly of a centrin-transducin complex in the connecting cilium of photoreceptor cells may regulate these transducin translocations. Here we demonstrate expression of all four known, closely related centrin isoforms in the mammalian retina. Interaction assays revealed binding potential of the four centrin isoforms to Gtbetagamma heterodimers. High affinity b…
Dis-organizing centrosomal clusters: specific cancer therapy for a generic spread?
2015
Cancer is a leading cause of mortality and the annual incidence of new cancer cases is rising worldwide. Due to the frequent development of resistance and the side effects of established anti-cancer drugs, the quest for new drugs with improved therapeutic features goes on. In contrast to cytotoxic chemotherapy of the past, the concept of targeted chemotherapy attempts to increase specificity of therapy by attacking tumor-related mechanisms. A novel emerging treatment concept represents the inhibition of centrosomal clustering. The centrosome regulates mitotic spindle formation assuring uniform separation of chromosomes to daughter cells. Many tumors contain supernumerary centrosomes, which …
RNAi mediated acute depletion of Retinoblastoma protein (pRb) promotes aneuploidy in human primary cells via micronuclei formation
2009
BACKGROUND: Changes in chromosome number or structure as well as supernumerary centrosomes and multipolar mitoses are commonly observed in human tumors. Thus, centrosome amplification and mitotic checkpoint dysfunctions are believed possible causes of chromosomal instability. The Retinoblastoma tumor suppressor (RB) participates in the regulation of synchrony between DNA synthesis and centrosome duplication and it is involved in transcription regulation of some mitotic genes. Primary human fibroblasts were transfected transiently with short interfering RNA (siRNA) specific for human pRb to investigate the effects of pRb acute loss on chromosomal stability. RESULTS: Acutely pRb-depleted fibr…
Simultaneous Aurora-A/STK15 overexpression and centrosome amplification induce chromosomal instability in tumour cells with a MIN phenotype
2007
Abstract Background Genetic instability is a hallmark of tumours and preneoplastic lesions. The predominant form of genome instability in human cancer is chromosome instability (CIN). CIN is characterized by chromosomal aberrations, gains or losses of whole chromosomes (aneuploidy), and it is often associated with centrosome amplification. Centrosomes control cell division by forming a bipolar mitotic spindle and play an essential role in the maintenance of chromosomal stability. However, whether centrosome amplification could directly cause aneuploidy is not fully established. Also, alterations in genes required for mitotic progression could be involved in CIN. A major candidate is represe…
Centrosome amplification mediates small extracellular vesicles secretion via lysosome disruption
2020
SummaryBidirectional communication between cells and their surrounding environment is critical in both normal and pathological settings. Extracellular vesicles (EVs), which facilitate the horizontal transfer of molecules between cells, are recognized as an important constituent of cell-cell communication. In cancer, alterations in EV secretion contribute to the growth and metastasis of tumor cells. However, the mechanisms underlying these changes remain largely unknown. Here, we show that centrosome amplification is associated with and sufficient to promote small extracellular vesicle (SEV) secretion in pancreatic cancer cells. This is a direct result due of lysosomal dysfunction, caused by…
Constitutive hsp70 is essential to mitosis during early cleavage of Paracentrotus lividus embryos: The blockage of constitutive hsp70 impairs mitosis
1999
Localization of constitutive hsp70 in eggs and early embryos of sea urchin Paracentrotus lividus is shown by means of in situ immunostaining. An accumulation of this protein is shown in the mitotic structures (asters, spindles and centrosomes). Microinjection of anti-hsp70 antibodies into eggs causes impairment of formation of mitotic structures and of cell division. This impairment goes from a complete mitotic block, to irregular mitotic apparatus formation with irregular cleavage, depending upon the antibody concentration. The localization of hsp70 after antibody microinjection is also described. Blockage of mitotic apparatus formation by nocodazole also blocks the concentration of hsp70 …
Aurora-A Is Essential for the Tumorigenic Capacity and Chemoresistance of Colorectal Cancer Stem Cells
2010
Abstract Colorectal cancer stem cells (CR-CSC) are responsible for the generation and maintenance of intestinal tumors and are highly resistant to conventional chemotherapeutic agents. Aurora-A, a serine-threonine kinase involved in mitosis regulation, plays multiple key functions in tumor initiation and progression. We found that Aurora-A is overexpressed in primary colorectal tumor cells, in the CR-CSC fraction, and in stem cell–derived differentiated cells, compared with normal colon tissue. Aurora-A expression was functionally linked to centrosome amplification in CR-CSC, as indicated by the decrease in cells with multiple centrosomes that followed Aurora-A silencing. Knockdown of Auror…