Glioma progression through the prism of heat shock protein mediated extracellular matrix remodeling and epithelial to mesenchymal transition

Rajesh, Y.; Biswas, Angana; Mandal, Mahitosh

doi:10.1016/j.yexcr.2017.08.032

Cited by 40 publications

(36 citation statements)

References 122 publications

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“…By elucidating the molecular pathways involved in gliomagenesis, it could be possible to identify promising GBM-specific therapeutic targets and use these as part of a developmental platform to advance effective therapies for this consistently fatal cancer [2,3]. Heat shock proteins (HSPs) have been extensively studied and provide a primary protein signature for GBM progression [4]. HSPs serve as a nexus for ECM remodeling and EMT, which are elevated in both acquired radiation and temozolomide resistance in GBM cells [4].…”

Section: Discussionmentioning

confidence: 99%

“…Defining the underpinnings of GBM development and progression has potential to provide a path forward in creating effective GBM therapies [1,3]. Omics studies in search of protein signatures and biomarkers for GBM specifically highlight upregulation of heat shock proteins (HSPs) in GBM [1,4]. The HSPs promote tumor growth by stimulating cell proliferation and inhibiting cell death pathways [4].…”

Section: Introductionmentioning

confidence: 99%

“…Omics studies in search of protein signatures and biomarkers for GBM specifically highlight upregulation of heat shock proteins (HSPs) in GBM [1,4]. The HSPs promote tumor growth by stimulating cell proliferation and inhibiting cell death pathways [4]. They also display chaperone activity for many proteins including matrix degrading enzymes involved in extracellular matrix (ECM) degradation.…”

Section: Introductionmentioning

confidence: 99%

“…HSPs also play an essential extracellular role during the infiltrative phase in GBM through binding to MMPs [5]. A potential role for HSPs in facilitating epithelial-mesenchymal transition (EMT) in cancer has also been reported [4]. HSP up regulation is evident in gliomagenesis as well as in acquisition of radio-(radiation) and temozolomide-(TMZ) resistance (radio/ TMZR) [4].…”

Section: Introductionmentioning

confidence: 99%

“…A potential role for HSPs in facilitating epithelial-mesenchymal transition (EMT) in cancer has also been reported [4]. HSP up regulation is evident in gliomagenesis as well as in acquisition of radio-(radiation) and temozolomide-(TMZ) resistance (radio/ TMZR) [4]. Hence, HSPs represent prospective targets to develop effective clinical strategies for advancing rational anti-GBM drug development.…”

Section: Introductionmentioning

confidence: 99%

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Transcriptional regulation of HSPB1 by Friend leukemia integration-1 factor modulates radiation and temozolomide resistance in glioblastoma

et al. 2020

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Glioblastoma (GBM) is the most common primary brain tumor and is invariably fatal. Heat shock proteins (HSPs) provide protein signatures/biomarkers for GBM that afford potential as targets for developing anti-GBM drugs. In GBM, elevated expression of hypoxia inducible factors under the influence of Ets family proteins significantly promotes the expression of HSPs. RNAseq analysis identified HSPB1 as a prominent upregulated HSP in GBM and in radiation resistant/temozolomide resistant (radio/TMZR) GBM. Here, we established friend leukemia integration 1 (Fli-1), a member of Ets family to be playing a transcriptional regulatory role on the HSPB1 gene. Fli-1 binds to nucleotide residues GGAA at binding sites 3, 6 and 7 in the 5-kb upstream region of HSPB1. Fli-1 has been linked to oncogenic transformation with upregulation in radio/TMZR GBM. Overexpression of Fli-1 in GBM promotes resistance, whereas Fli-1 knockdown in radio/TMZR GBM cells suppresses resistance. We identify the underlying molecular mechanisms of Fli-1-mediated regulation of HSPB1 that drive extracellular matrix remodeling and epithelial to mesenchymal transition in radio/TMZR GBM cells. This study uncovers Fli-1 as a potential therapeutic target for combating radiation and temozolomide resistance in GBM.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Transcriptional regulation of HSPB1 by Friend leukemia integration-1 factor modulates radiation and temozolomide resistance in glioblastoma

et al. 2020

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Spatial Dissection of Invasive Front from Tumor Mass Enables Discovery of Novel microRNA Drivers of Glioblastoma Invasion

Huang

Kogiso

et al. 2021

Advanced Science

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Diffuse invasion is the primary cause of treatment failure of glioblastoma (GBM). Previous studies on GBM invasionhave long been forced to use the resected tumor mass cells. Here, a strategy to reliably isolate matching pairs of invasive (GBM INV ) and tumor core (GBM TC ) cells from the brains of 6 highly invasive patient-derived orthotopic models is described. Direct comparison of these GBM INV and GBM TC cells reveals a significantly elevated invasion capacity in GBM INV cells, detects 23/768 miRNAs over-expressed in the GBM INV cells (miRNA INV ) and 22/768 in the GBM TC cells (miRNA TC ), respectively. Silencing the top 3 miRNAs INV (miR-126, miR-369-5p, miR-487b) successfully blocks invasion of GBM INV cells in vitro and in mouse brains. Integrated analysis with mRNA expression identifies miRNA INV target genes and discovers KCNA1 as the sole common computational target gene of which 3 inhibitors significantly suppress invasion in vitro. Furthermore, in vivo treatment with 4-aminopyridine (4-AP) effectively eliminates GBM invasion and significantly prolongs animal survival times (P = 0.035). The results highlight the power of spatial dissection of functionally accurate GBM INV and GBM TC cells in identifying novel drivers of GBM invasion and provide strong rationale to support the use of biologically accurate starting materials in understanding cancer invasion and metastasis.

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Identification of genes related to low‐grade glioma progression and prognosis based on integrated transcriptome analysis

Jiang

Guo

et al. 2019

J of Cellular Biochemistry

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Glioma is one of the most common types of human brain tumor, with high mortality in high-grade gliomas (HGG). Low-grade gliomas (LGG) can progress into HGG, leading to poor prognosis. However, it is unclear what factors affect the progression of LGG to HGG. This study aims to explore the function of the crosstalk genes on the progression and prognosis of LGG using bioinformatics analysis. Integrated transcriptome analysis was used to screen differentially expressed genes (DEGs). Then, gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to investigate the association between DEGs and gene functions and pathways by ClusterProfiler package and ClueGO plug-in. Protein-protein interaction (PPI) network analysis was applied to explore the connection between genes and biological processes. Subsequently, the gene clusters were analyzed using the Centiscape and molecular complex detection (MCODE) plug-in in Cytoscape software, where the crosstalk genes were identified for further study. Ultimately, the UALCAN website and Gene Expression Profiling Interactive Analysis (GEPIA) website were performed to visualize the expression levels and survival curves of genes, respectively. There were 74DEGs identified in glioma, including 55 upregulated genes and 19 downregulated genes, which mainly were enriched in extracellular matrix (ECM)receptor interaction, focal adhesion, PI3K-Akt signaling pathway, and so on. Then, six crosstalk genes were selected, including COL1A1, COL1A2, COL3A1, COL4A1, COL4A2, and COL5A2 genes. Overall survival (OS) analysis of crosstalk genes was conducted on the GEPIA website. High expression levels of crosstalk genes were closely related to the low survival rate of patients withLGG. The overexpressed crosstalk genes, such as COL1A1, COL1A2, COL3A1, COL4A1, COL4A2, and COL5A2 may participate in the progression and poor prognosis of LGG through the ECM-receptor interaction pathway. K E Y W O R D S bioinformatics, crosstalk genes, glioma, prognosis, progression Yongcan Guo and Hualin Tao contributed equally to this study.Glioma is the most common primary tumor of the central nervous system, 1 diagnosed based on pathological grade and molecular subtype. And gliomas are classified into grades I to IV by World Health Organization (WHO), including low-grade (WHO grades I-II) and high-grade (WHO grades III-IV) gliomas. 2 High-grade gliomas (HGG) have a high mortality rate and low five-year survival rate with less than 10%. 3 The effect of radiotherapy and chemotherapy is not obvious for HGG, leading to the median survival time of 14 to 17 months, 4 less than the low-grade glioma (LGG), of which the average survival time is approximately 10 years. By contrast, in case the LGG progress into HGG, the mortality rate will increase. 5 Therefore, it is necessary to explore the factors that have an influence on the progression of LGG to HGG, aiming at slowing down the progression and extending survival time of patients with LGG. In recent years, most ...

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Glioma progression through the prism of heat shock protein mediated extracellular matrix remodeling and epithelial to mesenchymal transition

Cited by 40 publications

References 122 publications

Transcriptional regulation of HSPB1 by Friend leukemia integration-1 factor modulates radiation and temozolomide resistance in glioblastoma

Transcriptional regulation of HSPB1 by Friend leukemia integration-1 factor modulates radiation and temozolomide resistance in glioblastoma

Spatial Dissection of Invasive Front from Tumor Mass Enables Discovery of Novel microRNA Drivers of Glioblastoma Invasion

Identification of genes related to low‐grade glioma progression and prognosis based on integrated transcriptome analysis

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