uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Proteins of the Wnt signaling pathway as targets for the regulation of CD133(+) cancer stem cells in glioblastoma
Far Eastern Fed Univ, Sch Biomed, 8 Sukhanova St, Vladivostok 690091, Russia;Minist Hlth Russia, NN Blokhin Natl Med Res Ctr Oncol, Moscow 115478, Russia.
Minist Hlth Russia, NN Blokhin Natl Med Res Ctr Oncol, Moscow 115478, Russia.
Far Eastern Fed Univ, Sch Biomed, 8 Sukhanova St, Vladivostok 690091, Russia.
Far Eastern Fed Univ, Sch Biomed, 8 Sukhanova St, Vladivostok 690091, Russia.
Show others and affiliations
2019 (English)In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 41, no 5, p. 3080-3088Article in journal (Refereed) Published
Abstract [en]

Glioblastoma multiforme (GBM) is one of the most aggressive types of brain tumor and is highly resistant to therapy. The median survival time for patients with GBM is 15 months. GBM resistance to treatment is associated with cancer stem cells (CSCs). CD133 membrane glycoprotein is the best-known marker of GBM CSCs. The Wnt signaling pathway plays an important role in the proliferation of all stem cells. To the best of our knowledge, the present study was the first to examine the expression levels of proteins associated with the Wnt signaling pathway in CD133(+) CSCs of human GBM. Furthermore, potential targets that may regulate CD133(+) CSCs in human GBM were investigated. The human GBM U-87MG cell line was cultured in neurobasal medium supplemented with B27, fibroblast growth factor, epidermal growth factor and no serum. Immunohistochemical characteristics of glioma spheres were investigated based on the expression of key markers of CSCs. CD133(+) cells were extracted from glioma spheres by cell sorting and then lysed. High-performance liquid chromatography-mass spectrometry was used for proteome analysis. Lysates of CD133(-) cells in GBM were used for comparison. The present study was the first to describe the conceptual proteome differences between GBM and CD133(+) CSCs of the common pool. Major differences were identified in the glycolysis/gluconeogenesis, focal adhesion, tight junction and Wnt signaling pathways. This study aimed to analyze the crucial role that proteins of the Wnt signaling pathway play in stem cell proliferation. The identified proteins were analyzed for their association with the Wnt signaling pathway using the international open databases PubMed, Protein Analysis Through Evolutionary Relationships, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and Search Tool for the Retrieval of Interacting Genes/Proteins. An increased expression of 12 proteins associated with the Wnt signaling pathway were identified in GBM CD133(+) CSCs, which included catenin beta-1, disheveled associated activator of morphogenesis 1, RAC family small GTPase 2 and RAS homolog gene family member A, a number of which are also associated with adherens junctions. The Wnt signaling pathway is not upregulated in CSCs; however, the high expression levels of adenomatous polyposis coli, beta-catenin, C-terminal binding protein (CtBP) and RuvB-like AAA ATPase 1 (RUVBL1 or Pontin52) proteins suggest the possibility of alternative activation of specific genes in the nuclei of these cells. Calcyclin-binding protein, casein kinase II alpha, casein kinase II beta, CtBP1, CtBP2, CUL1 and RUVBL1 proteins may be used as targets for the pharmaceutical regulation of CSCs in complex GBM treatment.

Place, publisher, year, edition, pages
SPANDIDOS PUBL LTD , 2019. Vol. 41, no 5, p. 3080-3088
Keywords [en]
glioblastoma multiforme, CD133(+) cancer stem cells, Wnt signaling pathway
National Category
Cell Biology
Identifiers
URN: urn:nbn:se:uu:diva-382547DOI: 10.3892/or.2019.7043ISI: 000464015900043PubMedID: 30864699OAI: oai:DiVA.org:uu-382547DiVA, id: diva2:1314975
Available from: 2019-05-10 Created: 2019-05-10 Last updated: 2019-05-10Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed

Authority records BETA

Sharma, Hary Shanker

Search in DiVA

By author/editor
Sharma, Hary Shanker
By organisation
Anaesthesiology and Intensive Care
In the same journal
Oncology Reports
Cell Biology

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 14 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf