NDLI: Prion protein regulates invasiveness in glioblastoma stem cells

Content Provider	Springer Nature : BioMed Central
Author	Prado, Mariana B. Coelho, Bárbara P. Iglesia, Rebeca P. Alves, Rodrigo N. Boccacino, Jacqueline M. Fernandes, Camila F. L. Melo-Escobar, Maria Isabel Ayyadhury, Shamini Cruz, Mario C. Santos, Tiago G. Beraldo, Flávio H. Fan, Jue Ferreira, Frederico M. Nakaya, Helder I. Prado, Marco A. M. Prado, Vania F. Duennwald, Martin L. Lopes, Marilene H.
Abstract	Background Glioblastoma (GBM) is an aggressive brain tumor driven by glioblastoma stem cells (GSCs), which represent an appealing target for therapeutic interventions. The cellular prion protein (PrPC), a scaffold protein involved in diverse cellular processes, interacts with various membrane and extracellular matrix molecules, influencing tumor biology. Herein, we investigate the impact of PrPC expression on GBM. Methods To address this goal, we employed CRISPR-Cas9 technology to generate PrPC knockout (KO) glioblastoma cell lines, enabling detailed loss-of-function studies. Bulk RNA sequencing followed by differentially expressed gene and pathway enrichment analyses between U87 or U251 PrPC-wild-type (WT) cells and PrPC-knockout (KO) cells were used to identify pathways regulated by PrPC. Immunofluorescence assays were used to evaluate cellular morphology and protein distribution. For assessment of protein levels, Western blot and flow cytometry assays were employed. Transwell and growth curve assays were used to determine the impact of loss-of-PrPC in GBM invasiveness and proliferation, respectively. Single-cell RNA sequencing analysis of data from patient tumors from The Cancer Genome Atlas (TCGA) and the Broad Institute of Single-Cell Data Portal were used to evaluate the correspondence between our in vitro results and patient samples. Results Transcriptome analysis of PrPC-KO GBM cell lines revealed altered expression of genes associated with crucial tumor progression pathways, including migration, proliferation, and stemness. These findings were corroborated by assays that revealed impaired invasion, migration, proliferation, and self-renewal in PrPC-KO GBM cells, highlighting its critical role in sustaining tumor growth. Notably, loss-of-PrPC disrupted the expression and localization of key stemness markers, particularly CD44. Additionally, the modulation of PrPC levels through CD44 overexpression further emphasizes their regulatory role in these processes. Conclusions These findings establish PrPC as a modulator of essential molecules on the cell surface of GSCs, highlighting its potential as a therapeutic target for GBM.
Related Links	https://bmccancer.biomedcentral.com/counter/pdf/10.1186/s12885-024-13285-4.pdf
Ending Page	17
Page Count	17
Starting Page	1
File Format	HTM / HTML
ISSN	14712407
DOI	10.1186/s12885-024-13285-4
Journal	BMC Cancer
Issue Number	1
Volume Number	24
Language	English
Publisher	BioMed Central
Publisher Date	2024-12-18
Access Restriction	Open
Subject Keyword	Cancer Research Oncology Surgical Oncology Health Promotion and Disease Prevention Biomedicine Medicine Public Health Cellular prion protein Glioblastoma stem cells CD44 Invasion Migration Medicine/Public Health
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology Genetics
Journal Impact Factor	3.4/2023
5-Year Journal Impact Factor	3.8/2023

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

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