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Engagement of cellular prion protein with the co-chaperone Hsp70/90 organizing protein regulates the proliferation of glioblastoma stem-like cells

Overview of attention for article published in Stem Cell Research & Therapy, April 2017
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4 tweeters

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20 Dimensions

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42 Mendeley
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Title
Engagement of cellular prion protein with the co-chaperone Hsp70/90 organizing protein regulates the proliferation of glioblastoma stem-like cells
Published in
Stem Cell Research & Therapy, April 2017
DOI 10.1186/s13287-017-0518-1
Pubmed ID
Authors

Rebeca Piatniczka Iglesia, Mariana Brandão Prado, Lilian Cruz, Vilma Regina Martins, Tiago Góss Santos, Marilene Hohmuth Lopes

Abstract

Glioblastoma (GBM), a highly aggressive brain tumor, contains a subpopulation of glioblastoma stem-like cells (GSCs) that play roles in tumor maintenance, invasion, and therapeutic resistance. GSCs are therefore a promising target for GBM treatment. Our group identified the cellular prion protein (PrP(C)) and its partner, the co-chaperone Hsp70/90 organizing protein (HOP), as potential target candidates due to their role in GBM tumorigenesis and in neural stem cell maintenance. GSCs expressing different levels of PrP(C) were cultured as neurospheres with growth factors, and characterized with stem cells markers and adhesion molecules markers through immunofluorescence and flow cytometry. We than evaluated GSC self-renewal and proliferation by clonal density assays and BrdU incorporation, respectively, in front of recombinant HOP treatment, combined or not with a HOP peptide which mimics the PrP(C) binding site. Stable silencing of HOP was also performed in parental and/or PrP(C)-depleted cell populations, and proliferation in vitro and tumor growth in vivo were evaluated. Migration assays were performed on laminin-1 pre-coated glass. We observed that, when GBM cells are cultured as neurospheres, they express specific stemness markers such as CD133, CD15, Oct4, and SOX2; PrP(C) is upregulated compared to monolayer culture and co-localizes with CD133. PrP(C) silencing downregulates the expression of molecules associated with cancer stem cells, upregulates markers of cell differentiation and affects GSC self-renewal, pointing to a pivotal role for PrP(C) in the maintenance of GSCs. Exogenous HOP treatment increases proliferation and self-renewal of GSCs in a PrP(C)-dependent manner while HOP knockdown disturbs the proliferation process. In vivo, PrP(C) and/or HOP knockdown potently inhibits the growth of subcutaneously implanted glioblastoma cells. In addition, disruption of the PrP(C)-HOP complex by a HOP peptide, which mimics the PrP(C) binding site, affects GSC self-renewal and proliferation indicating that the HOP-PrP(C) complex is required for GSC stemness. Furthermore, PrP(C)-depleted GSCs downregulate cell adhesion-related proteins and impair cell migration indicating a putative role for PrP(C) in the cell surface stability of cell adhesion molecules and GBM cell invasiveness, respectively. In conclusion, our results show that the modulation of HOP-PrP(C) engagement or the decrease of PrP(C) and HOP expression may represent a potential therapeutic intervention in GBM, regulating glioblastoma stem-like cell self-renewal, proliferation, and migration.

Twitter Demographics

The data shown below were collected from the profiles of 4 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 42 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 42 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 9 21%
Student > Bachelor 8 19%
Researcher 4 10%
Professor > Associate Professor 4 10%
Student > Postgraduate 2 5%
Other 5 12%
Unknown 10 24%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 9 21%
Agricultural and Biological Sciences 6 14%
Medicine and Dentistry 5 12%
Neuroscience 4 10%
Economics, Econometrics and Finance 2 5%
Other 5 12%
Unknown 11 26%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 25 April 2017.
All research outputs
#5,206,867
of 9,724,738 outputs
Outputs from Stem Cell Research & Therapy
#469
of 863 outputs
Outputs of similar age
#135,604
of 262,234 outputs
Outputs of similar age from Stem Cell Research & Therapy
#18
of 29 outputs
Altmetric has tracked 9,724,738 research outputs across all sources so far. This one is in the 43rd percentile – i.e., 43% of other outputs scored the same or lower than it.
So far Altmetric has tracked 863 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.0. 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 262,234 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 44th percentile – i.e., 44% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 29 others from the same source and published within six weeks on either side of this one. This one is in the 31st percentile – i.e., 31% of its contemporaries scored the same or lower than it.