Could We Address the Interplay Between CD133, Wnt/β-Catenin, and TERT Signaling Pathways as a Potential Target for Glioblastoma Therapy?

Behrooz, Amir Barzegar; Syahir, Amir

doi:10.3389/fonc.2021.642719

Cited by 26 publications

(21 citation statements)

References 89 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Targeting CTNNB1 in the Wnt pathway can inhibit the stemness and/or malignant cellular phenotypes of glioma considered as a therapeutic target for the treatment of GBM. 54 , 55 …”

Section: Resultsmentioning

confidence: 99%

“…The involvement of CTNNB1 in the Wnt signaling pathway facilitates GBM formation, and stemness and leads to drug resistance. Targeting CTNNB1 in the Wnt pathway can inhibit the stemness and/or malignant cellular phenotypes of glioma considered as a therapeutic target for the treatment of GBM. , …”

Section: Resultsmentioning

confidence: 99%

“…Targeting CTNNB1 in the Wnt pathway can inhibit the stemness and/or malignant cellular phenotypes of glioma considered as a therapeutic target for the treatment of GBM. 54,55 An epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase that spans the cell membrane and gets activated by different types of ligands. The activated EGFR stimulates autophosphorylation of tyrosine residues, eliciting the activation of downstream pathways, which leads to cell growth, proliferation, DNA synthesis, and survival.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Integrated Transcriptome Profiling Identifies Prognostic Hub Genes as Therapeutic Targets of Glioblastoma: Evidenced by Bioinformatics Analysis

Nayak

2022

ACS Omega

View full text Add to dashboard Cite

Glioblastoma (GBM) is the most devastating and frequent type of primary brain tumor with high morbidity and mortality. Despite the use of surgical resection followed by radio- and chemotherapy as standard therapy, the progression of GBM remains dismal with a median overall survival of <15 months. GBM embodies a populace of cancer stem cells (GSCs) that is associated with tumor initiation, invasion, therapeutic resistance, and post-treatment reoccurrence. However, understanding the potential mechanisms of stemness and their candidate biomarkers remains limited. Hence in this investigation, we aimed to illuminate potential candidate hub genes and key pathways associated with the pathogenesis of GSC in the development of GBM. The integrated analysis discovered differentially expressed genes (DEGs) between the brain cancer tissues (GBM and GSC) and normal brain tissues. Multiple approaches, including gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, were employed to functionally annotate the DEGs and visualize them through the R program. The significant hub genes were identified through the protein–protein interaction network, Venn diagram analysis, and survival analysis. We observed that the upregulated DEGs were prominently involved in the ECM–receptor interaction pathway. The downregulated genes were mainly associated with the axon guidance pathway. Five significant hub genes (CTNNB1, ITGB1, TNC, EGFR, and SHOX2) were screened out through multiple analyses. GO and KEGG analyses of hub genes uncovered that these genes were primarily enriched in disease-associated pathways such as the inhibition of apoptosis and the DNA damage repair mechanism, activation of the cell cycle, EMT (epithelial–mesenchymal transition), hormone AR (androgen receptor), hormone ER (estrogen receptor), PI3K/AKT (phosphatidylinositol 3-kinase and AKT), RTK (receptor tyrosine kinase), and TSC/mTOR (tuberous sclerosis complex and mammalian target of rapamycin). Consequently, the epigenetic regulatory network disclosed that hub genes played a vital role in the progression of GBM. Finally, candidate drugs were predicted that can be used as possible drugs to treat GBM patients. Overall, our investigation offered five hub genes (CTNNB1, ITGB1, TNC, EGFR, and SHOX2) that could be used as precise diagnostic and prognostic candidate biomarkers of GBM and might be used as personalized therapeutic targets to obstruct gliomagenesis.

show abstract

“…Targeting CTNNB1 in the Wnt pathway can inhibit the stemness and/or malignant cellular phenotypes of glioma considered as a therapeutic target for the treatment of GBM. 54 , 55 …”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: ■ Results and Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Integrated Transcriptome Profiling Identifies Prognostic Hub Genes as Therapeutic Targets of Glioblastoma: Evidenced by Bioinformatics Analysis

Nayak

2022

ACS Omega

View full text Add to dashboard Cite

show abstract

“…Aberrant hyperactivation of the Wnt signaling pathway, whose causes can include mutations in APC, β-catenin, WTX, and TCF4, is implicated in tumor growth, recurrence, and self-renewal of GSCs [ 117 ]. The Wnt pathway has also been implicated in GBM resistance to TMZ and RT [ 118 ].…”

Section: Signal Transduction Pathwaysmentioning

confidence: 99%

Molecular Pathways and Genomic Landscape of Glioblastoma Stem Cells: Opportunities for Targeted Therapy

Hersh

Gaitsch

Alomari

et al. 2022

Cancers

View full text Add to dashboard Cite

Glioblastoma (GBM) is an aggressive tumor of the central nervous system categorized by the World Health Organization as a Grade 4 astrocytoma. Despite treatment with surgical resection, adjuvant chemotherapy, and radiation therapy, outcomes remain poor, with a median survival of only 14-16 months. Although tumor regression is often observed initially after treatment, long-term recurrence or progression invariably occurs. Tumor growth, invasion, and recurrence is mediated by a unique population of glioblastoma stem cells (GSCs). Their high mutation rate and dysregulated transcriptional landscape augment their resistance to conventional chemotherapy and radiation therapy, explaining the poor outcomes observed in patients. Consequently, GSCs have emerged as targets of interest in new treatment paradigms. Here, we review the unique properties of GSCs, including their interactions with the hypoxic microenvironment that drives their proliferation. We discuss vital signaling pathways in GSCs that mediate stemness, self-renewal, proliferation, and invasion, including the Notch, epidermal growth factor receptor, phosphatidylinositol 3-kinase/Akt, sonic hedgehog, transforming growth factor beta, Wnt, signal transducer and activator of transcription 3, and inhibitors of differentiation pathways. We also review epigenomic changes in GSCs that influence their transcriptional state, including DNA methylation, histone methylation and acetylation, and miRNA expression. The constituent molecular components of the signaling pathways and epigenomic regulators represent potential sites for targeted therapy, and representative examples of inhibitory molecules and pharmaceuticals are discussed. Continued investigation into the molecular pathways of GSCs and candidate therapeutics is needed to discover new effective treatments for GBM and improve survival.

show abstract

“…It has been shown that CD133 can activate the Wnt/b-catenin pathway, maintaining the cancer stem cell population in glioblastoma. Indeed, the expression level of Wnt/b-catenin-related signals in CD133-positive cancer stem cells has been substantially increased compared to differentiated CD133-negative glioblastoma cells (9). Growing evidence indicates that CD133 can increase proliferation, induce cancer therapy resistance, and maintain stemness in glioblastoma (10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

The Prognostic Value of CD133 in Predicting the Relapse and Recurrence Pattern of High-Grade Gliomas on MRI: A Meta-Analysis

et al. 2021

View full text Add to dashboard Cite

BackgroundCancer stem cells have been implicated in tumor relapse, tumor invasion, and cancer therapy resistance in high-grade gliomas; thus, characterizing cancer stem cell-related markers can help determine the prognosis of affected patients. Preclinical studies have reported that CD133 is implicated in tumor recurrence and cancer therapy resistance in high-grade gliomas; however, clinical studies have reported inconclusive results regarding its prognostic value in patients with high-grade gliomas.MethodsWe systematically searched the PubMed, Scopus, Web of Science, and Embase databases to obtain peer-reviewed studies published before March 10, 2021. Then, we conducted the current systematic review and meta-analysis based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statements. By applying the random-effect model, the effect size of studies investigating the progression-free survival (PFS), time to local recurrence (TTL), and time to distant recurrence (TTD) were calculated using RevMan version 5.4. The heterogeneity between the included studies was studied by the I2 index and Cochran’s Q test. Egger test was performed on funnel plots to investigate the potential asymmetry and publication bias among the included studies using CMA version 2.ResultsWith the 10% cut-off, CD133 protein overexpression is associated with the inferior PFS of patients with high-grade gliomas. Increased CD133 protein expression is associated with sooner distant tumor recurrence on MRI in glioblastoma patients and patients with high-grade gliomas and improved TTL on MRI in glioblastoma patients.ConclusionBased on the current evidence from 1086 patients with high-grade gliomas, CD133 overexpression is a valuable marker to predict tumor relapse and tumor recurrence patterns in patients with high-grade gliomas.

show abstract

Could We Address the Interplay Between CD133, Wnt/β-Catenin, and TERT Signaling Pathways as a Potential Target for Glioblastoma Therapy?

Cited by 26 publications

References 89 publications

Integrated Transcriptome Profiling Identifies Prognostic Hub Genes as Therapeutic Targets of Glioblastoma: Evidenced by Bioinformatics Analysis

Integrated Transcriptome Profiling Identifies Prognostic Hub Genes as Therapeutic Targets of Glioblastoma: Evidenced by Bioinformatics Analysis

Molecular Pathways and Genomic Landscape of Glioblastoma Stem Cells: Opportunities for Targeted Therapy

The Prognostic Value of CD133 in Predicting the Relapse and Recurrence Pattern of High-Grade Gliomas on MRI: A Meta-Analysis

Contact Info

Product

Resources

About