scholarly journals GTSE1 tunes microtubule stability for chromosome alignment and segregation through MCAK inhibition

2016 ◽  
Author(s):  
Shweta Bendre ◽  
Arnaud Rondelet ◽  
Conrad Hall ◽  
Nadine Schmidt ◽  
Yu-Chih Lin ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Chromosome Segregation ◽  
Genome Stability ◽  
Cancer Cell Lines ◽  
Dynamic Regulation ◽  
Spindle Positioning ◽  
Chromosome Missegregation ◽  
Microtubule Stability ◽  
Chromosome Alignment

AbstractThe dynamic regulation of microtubules during mitosis is critical for accurate chromosome segregation and genome stability. Cancer cell lines with hyperstabilized kinetochore microtubules have increased segregation errors and elevated chromosomal instability (CIN), but the genetic defects responsible remain largely unknown. The microtubule depolymerase MCAK can influence CIN through its impact on microtubule stability, but how its potent activity is controlled in cells remains unclear. Here we show that GTSE1, a protein found overexpressed in aneuploid cancer cell lines and tumours, regulates microtubule stability during mitosis by inhibiting MCAK microtubule depolymerase activity. Cells lacking GTSE1 have defects in chromosome alignment and spindle positioning due to microtubule instability caused by excess MCAK activity. Reducing GTSE1 levels in CIN cancer cell lines reduces chromosome missegregation defects, while artificially inducing GTSE1 levels in chromosomally stable cells elevates chromosome missegregation and CIN. Thus GTSE1 inhibition of MCAK activity regulates the balance of microtubule stability that determines the fidelity of chromosome alignment, segregation, and chromosomal stability.

scholarly journals GTSE1 tunes microtubule stability for chromosome alignment and segregation by inhibiting the microtubule depolymerase MCAK

2016 ◽  
Vol 215 (5) ◽  
pp. 631-647 ◽  
Author(s):  
Shweta Bendre ◽  
Arnaud Rondelet ◽  
Conrad Hall ◽  
Nadine Schmidt ◽  
Yu-Chih Lin ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Chromosome Segregation ◽  
Genome Stability ◽  
Cancer Cell Lines ◽  
Dynamic Regulation ◽  
Spindle Positioning ◽  
Chromosome Missegregation ◽  
Microtubule Stability ◽  
Chromosome Alignment

The dynamic regulation of microtubules (MTs) during mitosis is critical for accurate chromosome segregation and genome stability. Cancer cell lines with hyperstabilized kinetochore MTs have increased segregation errors and elevated chromosomal instability (CIN), but the genetic defects responsible remain largely unknown. The MT depolymerase MCAK (mitotic centromere-associated kinesin) can influence CIN through its impact on MT stability, but how its potent activity is controlled in cells remains unclear. In this study, we show that GTSE1, a protein found overexpressed in aneuploid cancer cell lines and tumors, regulates MT stability during mitosis by inhibiting MCAK MT depolymerase activity. Cells lacking GTSE1 have defects in chromosome alignment and spindle positioning as a result of MT instability caused by excess MCAK activity. Reducing GTSE1 levels in CIN cancer cell lines reduces chromosome missegregation defects, whereas artificially inducing GTSE1 levels in chromosomally stable cells elevates chromosome missegregation and CIN. Thus, GTSE1 inhibition of MCAK activity regulates the balance of MT stability that determines the fidelity of chromosome alignment, segregation, and chromosomal stability.

scholarly journals Delayed Chromosome Alignment to the Spindle Equator Increases the Rate of Chromosome Missegregation in Cancer Cell Lines

Biomolecules ◽  
2018 ◽  
Vol 9 (1) ◽  
pp. 10 ◽  
Author(s):  
Kinue Kuniyasu ◽  
Kenji Iemura ◽  
Kozo Tanaka
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Chromosome Missegregation ◽  
Spindle Poles ◽  
Anaphase Onset ◽  
Sister Chromatids ◽  
Chromosome Congression ◽  
Chromosome Alignment ◽  
In Cells

For appropriate chromosome segregation, kinetochores on sister chromatids have to attach to microtubules from opposite spindle poles (bi-orientation). Chromosome alignment at the spindle equator, referred to as congression, can occur through the attachment of kinetochores to the lateral surface of spindle microtubules, facilitating bi-orientation establishment. However, the contribution of this phenomenon to mitotic fidelity has not been clarified yet. Here, we addressed whether delayed chromosome alignment to the spindle equator increases the rate of chromosome missegregation. Cancer cell lines depleted of Kid, a chromokinesin involved in chromosome congression, showed chromosome alignment with a slight delay, and increased frequency of lagging chromosomes. Delayed chromosome alignment concomitant with an increased rate of lagging chromosomes was also seen in cells depleted of kinesin family member 4A (KIF4A), another chromokinesin. Cells that underwent chromosome missegregation took relatively longer time to align chromosomes in both control and Kid/KIF4A-depleted cells. Tracking of late-aligning chromosomes showed that they exhibit a higher rate of lagging chromosomes. Intriguingly, the metaphase of cells that underwent chromosome missegregation was shortened, and delaying anaphase onset ameliorated the increased chromosome missegregation. These data suggest that late-aligning chromosomes do not have sufficient time to establish bi-orientation, leading to chromosome missegregation. Our data imply that delayed chromosome alignment is not only a consequence, but also a cause of defective bi-orientation establishment, which can lead to chromosomal instability in cells without severe mitotic defects.

scholarly journals Dynamic regulation of CD24 and the invasive, CD44posCD24negphenotype in breast cancer cell lines

2009 ◽  
Vol 11 (6) ◽  
Author(s):  
Matthew J Meyer ◽  
Jodie M Fleming ◽  
Mustapha A Ali ◽  
Mitchell W Pesesky ◽  
Erika Ginsburg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Dynamic Regulation

scholarly journals Chromosome oscillation promotes Aurora A–dependent Hec1 phosphorylation and mitotic fidelity

2021 ◽  
Vol 220 (7) ◽  
Author(s):  
Kenji Iemura ◽  
Toyoaki Natsume ◽  
Kayoko Maehara ◽  
Masato T. Kanemaki ◽  
Kozo Tanaka
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Chromosomal Instability ◽  
Oscillation Amplitude ◽  
Cancer Cell Lines ◽  
Aurora A ◽  
Chromosome Missegregation ◽  
Phosphorylation Level ◽  
Chromosome Motion

Most cancer cells show chromosomal instability, a condition where chromosome missegregation occurs frequently. We found that chromosome oscillation, an iterative chromosome motion during metaphase, is attenuated in cancer cell lines. We also found that metaphase phosphorylation of Hec1 at serine 55, which is mainly dependent on Aurora A on the spindle, is reduced in cancer cell lines. The Aurora A–dependent Hec1-S55 phosphorylation level was regulated by the chromosome oscillation amplitude and vice versa: Hec1-S55 and -S69 phosphorylation by Aurora A is required for efficient chromosome oscillation. Furthermore, enhancement of chromosome oscillation reduced the number of erroneous kinetochore–microtubule attachments and chromosome missegregation, whereas inhibition of Aurora A during metaphase increased such errors. We propose that Aurora A–mediated metaphase Hec1-S55 phosphorylation through chromosome oscillation, together with Hec1-S69 phosphorylation, ensures mitotic fidelity by eliminating erroneous kinetochore–microtubule attachments. Attenuated chromosome oscillation and the resulting reduced Hec1-S55 phosphorylation may be a cause of CIN in cancer cell lines.

Abstract 4308: Dynamic regulation of CD24 and the invasive, CD44posCD24neg phenotype in breast cancer cell lines

2010 ◽  
Author(s):  
Matthew J. Meyer ◽  
Jodie M. Fleming ◽  
Mustapha A. Ali ◽  
Mitchell W. Pesesky ◽  
Erika Ginsburg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Dynamic Regulation

797: Noggin Blocks the Osteoinductive Properties of Human Prostate Cancer Cell Lines

2006 ◽  
Vol 175 (4S) ◽  
pp. 258-258
Author(s):  
Ruth Schwaninger ◽  
Cyrill A. Rentsch ◽  
Antoinette Wetterwald ◽  
Irena Klima ◽  
Gabri Van der Pluijm ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cancer Cell Lines ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Human Prostate Cancer Cell ◽  
Prostate Cancer Cell Lines
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