A Tale of Too Many Centrosomes

Acılan, Ceyda; Saunders, William S.

doi:10.1016/j.cell.2008.08.007

Cited by 38 publications

(36 citation statements)

References 21 publications

(31 reference statements)

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“…One mechanism of centrosome amplification mediated CIN is the clustering of the centrosomes into two centrosomal groups during mitosis to allow the formation of a bipolar spindle (4). Missegregation not only distorts the number of chromosomes in the daughter cells but also promotes or diminishes the expression of genes critical for cell viability and growth (1). The conventional wisdom has been that aneuploidy is a late event in cancer development, but recent evidence has suggested that aneuploidy is an early change for malignancy (22).…”

Section: Discussionmentioning

confidence: 99%

“…Centrosomes duplication is a crucial event when cell divided, which is indispensable for the formation of the bipolar mitotic spindle and plays an essential role in the maintenance of chromosomal stability (1). Recent developments have addressed the impact of numerical centrosomal amplification on the cellular changes associated with tumorigenesis and chromosomal segregational defects in the cancer cell (2).…”

Section: Introductionmentioning

confidence: 99%

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NF-κB induces abnormal centrosome amplification by upregulation of CDK2 in laryngeal squamous cell cancer

Liu

Ma²,

Lu³

et al. 2011

Int J Oncol

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Abstract. Centrosome amplification can drive chromosomal instability (CIN) which is a major source of tumor initiation. The present study aimed to investigate the impact of nuclear factor kappa B (NF-κB) on centrosome amplification of Hep-2 cells. Immunofluorescence was performed to display centrosomes. BAY11-7082 was used as an inhibitor of NF-κB to assess the inhibition of centrosome amplification, and cyclin-dependent kinase 2 (CDK2), ensuring cell cycle cycle coordination with centrosome cycle was detected by Western blotting. Furthermore, a 1556-bp fragment of the CDK2 promoter was analyzed using the TRANSFAC-TESS software. Luciferase assay, including a series of truncated CDK2 promoters and site mutations, was carried out to determine NF-κB binding sites in the CDK2 promoter. Electrophoresis mobility shift and chromatin immunoprecipitation assays were applied to confirm whether NF-κB indeed binds to the 5'-promoter region of the CDK2 gene. To reveal the clinical significance of CDK2 expression in laryngeal squamous cell cancer, mRNA and protein levels were assessed by RT-PCR and Western blotting, respectively. We found that the transcription factor NF-κB plays a role in centrosome amplification in Hep-2 cells. Centrosome amplification is reduced by inhibition of the NF-κB pathway. Moreover, expression of the p65 subunit of NF-κB is sufficient to promote centrosome amplification and increase in CDK2 protein levels. We further identified a functional NF-κB binding site located in the CDK2 promoter. Single mutation of the NF-κB site III (construct mutIII) however resulted in 76±5% (p<0.01) luciferase activity reduction. Electromobility shift assays and chromatin immunoprecipitaton results suggest that NF-κB indeed binds to this responsive element associating with CDK2 expression and centrosome amplification. RT-PCR and Western blotting results revealed that both mRNA and protein levels of CDK2 were significantly higher in tumor tissues than those in paired adjacent normal laryngeal tissues.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

NF-κB induces abnormal centrosome amplification by upregulation of CDK2 in laryngeal squamous cell cancer

Liu

Ma²,

Lu³

et al. 2011

Int J Oncol

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“…In many solid tumors and in hematological malignancies, an increase in centrosome numbers, a common feature referred to as centrosome amplification, often strongly correlates with aneuploidy, chromosomal instability and malignant behaviors (Acilan and Saunders, 2008;Chandhok and Pellman, 2009;Nigg, 2002;Kwon et al, 2008). A crucial cellular mechanism for minimizing the deleterious consequences of multiple centrosomes is the clustering of the extra centrosomes into bipolar spindles to avoid the adverse levels of aneuploidy during mitosis (Acilan and Saunders, 2008;Basto et al, 2008;Holland and Cleveland, 2009).…”

Section: Compartmentalized Mitotic and Meiotic Roles Of Kinesin-14mentioning

confidence: 99%

“…A crucial cellular mechanism for minimizing the deleterious consequences of multiple centrosomes is the clustering of the extra centrosomes into bipolar spindles to avoid the adverse levels of aneuploidy during mitosis (Acilan and Saunders, 2008;Basto et al, 2008;Holland and Cleveland, 2009).…”

Section: Compartmentalized Mitotic and Meiotic Roles Of Kinesin-14mentioning

confidence: 99%

Molecular mechanisms of kinesin-14 motors in spindle assembly and chromosome segregation

She

Yang

2017

Journal of Cell Science

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During eukaryote cell division, molecular motors are crucial regulators of microtubule organization, spindle assembly, chromosome segregation and intracellular transport. The kinesin-14 motors are evolutionarily conserved minus-end-directed kinesin motors that occur in diverse organisms from simple yeasts to higher eukaryotes. Members of the kinesin-14 motor family can bind to, crosslink or slide microtubules and, thus, regulate microtubule organization and spindle assembly. In this Commentary, we present the common subthemes that have emerged from studies of the molecular kinetics and mechanics of kinesin-14 motors, particularly with regard to their non-processive movement, their ability to crosslink microtubules and interact with the minus-and plusends of microtubules, and with microtubule-organizing center proteins. In particular, counteracting forces between minus-enddirected kinesin-14 and plus-end-directed kinesin-5 motors have recently been implicated in the regulation of microtubule nucleation. We also discuss recent progress in our current understanding of the multiple and fundamental functions that kinesin-14 motors family members have in important aspects of cell division, including the spindle pole, spindle organization and chromosome segregation.

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“…Multipolar spindles form by centrosome overduplication or inheritance of additional centrosomes from a previous cell cycle. Some cells correct spindle multipolarity by clustering centrosomes into a single spindle pole or by expelling them from the cell; some cells with multipolar spindles fail to complete mitosis (Acilan and Saunders, 2008). For cells that do not correct spindle multipolarity, progression through mitosis produces aneuploid daughter cells (Zyss and Gergely, 2009).…”

Section: Small Changes In Microtubule Regulation May Impair Chromosommentioning

confidence: 99%

Tumor suppressor interactions with microtubules: keeping cell polarity and cell division on track

Hernández

Tirnauer

2010

Disease Models &Amp; Mechanisms

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Tumor suppressor proteins protect cells and tissues from malignant transformation. Among their diverse actions, many of these proteins interact with the microtubule cytoskeleton. This review focuses on the interactions of several tumor suppressors with microtubules and speculates on how disruption of microtubule-dependent processes may contribute to cancer development and spread. We conclude that several tumor suppressors stabilize microtubules and organize microtubule arrays, functions that are likely to be important in preventing tumorigenesis. How tumor suppressors link microtubule stability with cell fate, and how their mutation affects the response of cancer cells to anti-microtubule chemotherapy drugs, remains unclear; these should prove fertile areas for future research.

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A Tale of Too Many Centrosomes

Cited by 38 publications

References 21 publications

NF-κB induces abnormal centrosome amplification by upregulation of CDK2 in laryngeal squamous cell cancer

NF-κB induces abnormal centrosome amplification by upregulation of CDK2 in laryngeal squamous cell cancer

Molecular mechanisms of kinesin-14 motors in spindle assembly and chromosome segregation

Tumor suppressor interactions with microtubules: keeping cell polarity and cell division on track

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