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Chromosomal instability induced by increased BIRC5/Survivin levels affects tumorigenicity of glioma cells

Overview of attention for article published in BMC Cancer, December 2017
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Title
Chromosomal instability induced by increased BIRC5/Survivin levels affects tumorigenicity of glioma cells
Published in
BMC Cancer, December 2017
DOI 10.1186/s12885-017-3932-y
Pubmed ID
Authors

Marina Conde, Susanne Michen, Ralf Wiedemuth, Barbara Klink, Evelin Schröck, Gabriele Schackert, Achim Temme

Abstract

Survivin, belonging to the inhibitor of apoptosis (IAP) gene family, is abundantly expressed in tumors. It has been hypothesized that Survivin facilitates carcinogenesis by inhibition of apoptosis resulting in improved survival of tumorigenic progeny. Additionally, Survivin plays an essential role during mitosis. Together with its molecular partners Aurora B, Borealin and inner centromere protein it secures bipolar chromosome segregation. However, whether increased Survivin levels contribute to progression of tumors by inducing chromosomal instability remains unclear. We overexpressed Survivin in U251-MG, SVGp12, U87-MG, HCT116 and p53-deficient U87-MGshp53 and HCT116p53-/- cells. The resulting phenotype was investigated by FACS-assisted cell cycle analysis, Western Blot analysis, confocal laser scan microscopy, proliferation assays, spectral karyotyping and in a U251-MG xenograft model using immune-deficient mice. Overexpression of Survivin affected cells with knockdown of p53, cells harboring mutant p53 and SV40 large T antigen, respectively, resulting in the increase of cell fractions harboring 4n and >4n DNA contents. Increased γH2AX levels, indicative of DNA damage were monitored in all Survivin-transduced cell lines, but only in p53 wild type cells this was accompanied by an attenuated S-phase entry and activation of p21waf/cip. Overexpression of Survivin caused a DNA damage response characterized by increased appearance pDNA-PKcs foci in cell nuclei and elevated levels of pATM S1981 and pCHK2 T68. Additionally, evolving structural chromosomal aberrations in U251-MG cells transduced with Survivin indicated a DNA-repair by non-homologous end joining recombination. Subcutaneous transplantation of U251-MG cells overexpressing Survivin and mycN instead of mycN oncogene alone generated tumors with shortened latency and decreased apoptosis. Subsequent SKY-analysis of Survivin/mycN-tumors revealed an increase in structural chromosomal aberrations in cells when compared to mycN-tumors. Our data suggest that increased Survivin levels promote adaptive evolution of tumors through combining induction of genetic heterogeneity with inhibition of apoptosis.

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The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 45 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 45 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 7 16%
Student > Master 7 16%
Student > Ph. D. Student 4 9%
Student > Doctoral Student 4 9%
Student > Bachelor 4 9%
Other 4 9%
Unknown 15 33%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 15 33%
Medicine and Dentistry 5 11%
Agricultural and Biological Sciences 2 4%
Neuroscience 2 4%
Psychology 1 2%
Other 1 2%
Unknown 19 42%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 December 2017.
All research outputs
#15,487,739
of 23,015,156 outputs
Outputs from BMC Cancer
#4,154
of 8,359 outputs
Outputs of similar age
#269,354
of 441,975 outputs
Outputs of similar age from BMC Cancer
#104
of 194 outputs
Altmetric has tracked 23,015,156 research outputs across all sources so far. This one is in the 22nd percentile – i.e., 22% of other outputs scored the same or lower than it.
So far Altmetric has tracked 8,359 research outputs from this source. They receive a mean Attention Score of 4.3. This one is in the 40th percentile – i.e., 40% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 441,975 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 30th percentile – i.e., 30% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 194 others from the same source and published within six weeks on either side of this one. This one is in the 38th percentile – i.e., 38% of its contemporaries scored the same or lower than it.