scholarly journals Chromosomally unstable tumor cells specifically require KIF18A for proliferation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Carolyn Marquis ◽  
Cindy L. Fonseca ◽  
Katelyn A. Queen ◽  
Lisa Wood ◽  
Sarah E. Vandal ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Mitotic Spindle ◽  
Chromosomal Instability ◽  
Triple Negative ◽  
Strongly Correlated ◽  
Multipolar Spindles ◽  
Dynamics And Control ◽  
Diploid Cells ◽  
And Control ◽  
Dynamics Characteristic

AbstractChromosomal instability (CIN) is a hallmark of tumor cells caused by changes in the dynamics and control of microtubules that compromise the mitotic spindle. Thus, CIN cells may respond differently than diploid cells to treatments that target mitotic spindle regulation. Here, we test this idea by inhibiting a subset of kinesin motor proteins involved in mitotic spindle control. KIF18A is required for proliferation of CIN cells derived from triple negative breast cancer or colorectal cancer tumors but is not required in near-diploid cells. Following KIF18A inhibition, CIN tumor cells exhibit mitotic delays, multipolar spindles, and increased cell death. Sensitivity to KIF18A knockdown is strongly correlated with centrosome fragmentation, which requires dynamic microtubules but does not depend on bipolar spindle formation or mitotic arrest. Our results indicate the altered spindle microtubule dynamics characteristic of CIN tumor cells can be exploited to reduce the proliferative capacity of CIN cells.

scholarly journals Chromosomally unstable tumor cells specifically require KIF18A for proliferation

2020 ◽  
Author(s):  
Carolyn Marquis ◽  
Cindy L. Fonseca ◽  
Katelyn A. Queen ◽  
Lisa Wood ◽  
Sarah E. Vandal ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Mitotic Spindle ◽  
Microtubule Dynamics ◽  
Strongly Correlated ◽  
Spindle Microtubule ◽  
Multipolar Spindles ◽  
Dynamics And Control ◽  
Diploid Cells ◽  
And Control ◽  
Dynamics Characteristic

SummaryChromosomal instability (CIN), characterized by frequent missegregation of chromosomes during mitosis, is a hallmark of tumor cells caused by changes in the dynamics and control of microtubules that comprise the mitotic spindle1–3. Thus, CIN tumor cells may respond differently than normal diploid cells to treatments that target mitotic spindle regulation. We tested this idea by inhibiting a subset of kinesin motor proteins that control spindle microtubule dynamics and mechanics but are not required for the proliferation of near-diploid cells. Our results indicated that KIF18A was required for proliferation of CIN cells derived from triple negative breast cancer or colorectal cancer tumors but was not required in near-diploid cells. CIN tumor cells exhibited mitotic delays, multipolar spindles due to centrosome fragmentation, and increased cell death following inhibition of KIF18A. Sensitivity to KIF18A knockdown was strongly correlated with centrosome fragmentation, which required dynamic microtubules but did not depend on bipolar spindle formation or mitotic arrest. Our results indicate the altered spindle microtubule dynamics characteristic of CIN tumor cells can be exploited to reduce the proliferative capacity of CIN cells.

scholarly journals Carcinogen treatment leads to mitotic defects and arrest in cancer and noncancer cells

2018 ◽  
Author(s):  
Rebecca G Hartling ◽  
Christian J Pacheco ◽  
Emily A Bystrak ◽  
Nicholas J Quintyne
Keyword(s):  
Estrogen Receptor ◽  
Mitotic Index ◽  
Cell Lines ◽  
Mitotic Spindle ◽  
Chromosomal Instability ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Chromosomal Rearrangements ◽  
Anaphase Bridges ◽  
Multipolar Spindles

Genomic instability can manifest due to both chromosomal rearrangements and gain and loss of entire chromosomes. One mechanism by which a carcinogen acts is by increasing the rate of mitotic spindle defects during proliferation. These defects can lead to chromosomal instability that manifest as lagging chromosomes, anaphase bridges, or multipolar spindles. While several mechanisms exist to rectify these errors prior to completion of mitosis, some cells will escape repair, while others will prematurely exit mitosis. Here we examine the effects of two carcinogenic molecules: Fulvestrant, a chemotherapeutic that functions as a selective estrogen receptor degrader, and vinyl chloride, a hydrocarbon used to produce PVC. We exposed two cancer lines, A549 and UPCI:SCC103, and one noncancer line, GM03349, to increasing concentrations of the carcinogen for increasing durations, up to 48 hours exposure. We found that exposure to the carcinogen lowered the mitotic index in the cancer cell lines, while raising it in the noncancer line. Concurrently, we observed massive increases in the frequency of mitotic defects, with the most significant increases seen in prevalence of lagging chromosomes in prometaphase and metaphase and anaphase bridges. Live cell imaging showed that the occurrence of either of these defects had the strongest correlation with the likelihood that the cell would fail to complete mitosis. We also show that washing out the carcinogen decreases the frequency of mitotic defects in all three cell lines, but the mitotic index does not recover in the cancer cells. These findings demonstrate that carcinogen-induced mitotic defects have marked effects on the proliferative population of cells in terms of potential for contributing to chromosomal instability or removal from that population.

scholarly journals Carcinogen treatment leads to mitotic defects and arrest in cancer and noncancer cells

2018 ◽  
Author(s):  
Rebecca G Hartling ◽  
Christian J Pacheco ◽  
Emily A Bystrak ◽  
Nicholas J Quintyne
Keyword(s):  
Estrogen Receptor ◽  
Mitotic Index ◽  
Cell Lines ◽  
Mitotic Spindle ◽  
Chromosomal Instability ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Chromosomal Rearrangements ◽  
Anaphase Bridges ◽  
Multipolar Spindles

Genomic instability can manifest due to both chromosomal rearrangements and gain and loss of entire chromosomes. One mechanism by which a carcinogen acts is by increasing the rate of mitotic spindle defects during proliferation. These defects can lead to chromosomal instability that manifest as lagging chromosomes, anaphase bridges, or multipolar spindles. While several mechanisms exist to rectify these errors prior to completion of mitosis, some cells will escape repair, while others will prematurely exit mitosis. Here we examine the effects of two carcinogenic molecules: Fulvestrant, a chemotherapeutic that functions as a selective estrogen receptor degrader, and vinyl chloride, a hydrocarbon used to produce PVC. We exposed two cancer lines, A549 and UPCI:SCC103, and one noncancer line, GM03349, to increasing concentrations of the carcinogen for increasing durations, up to 48 hours exposure. We found that exposure to the carcinogen lowered the mitotic index in the cancer cell lines, while raising it in the noncancer line. Concurrently, we observed massive increases in the frequency of mitotic defects, with the most significant increases seen in prevalence of lagging chromosomes in prometaphase and metaphase and anaphase bridges. Live cell imaging showed that the occurrence of either of these defects had the strongest correlation with the likelihood that the cell would fail to complete mitosis. We also show that washing out the carcinogen decreases the frequency of mitotic defects in all three cell lines, but the mitotic index does not recover in the cancer cells. These findings demonstrate that carcinogen-induced mitotic defects have marked effects on the proliferative population of cells in terms of potential for contributing to chromosomal instability or removal from that population.

PROJECT ON ELECTRONIC STEERING SYSYTEM

2018 ◽  
Vol 4 (5) ◽  
pp. 7
Author(s):  
Shivam Dwivedi ◽  
Prof. Vikas Gupta
Keyword(s):  
Steering System ◽  
Essential Elements ◽  
Variable Pressure ◽  
Passenger Cars ◽  
Control Techniques ◽  
Steering Mechanism ◽  
Dynamics And Control ◽  
Active Research ◽  
Electronic Steering ◽  
And Control

As the four-wheel steering (4WS) system has great potentials, many researchers' attention was attracted to this technique and active research was made. As a result, passenger cars equipped with 4WS systems were put on the market a few years ago. This report tries to identify the essential elements of the 4WS technology in terms of vehicle dynamics and control techniques. Based on the findings of this investigation, the report gives a mechanism of electronically controlling the steering system depending on the variable pressure applied on it. This enhances the controlling and smoothens the operation of steering mechanism.

Author response for "Dynamics and control of microgrids as a resiliency source"

2020 ◽  
Author(s):  
Lung-An Lee ◽  
Chen-Ching Liu ◽  
Yin Xu ◽  
Kevin P. Schneider ◽  
Francis K. Tuffner ◽  
...  
Keyword(s):  
Author Response ◽  
Dynamics And Control ◽  
And Control
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