Glioma-derived plasminogen activator inhibitor-1 (PAI-1) regulates the recruitment of LRP1 positive mast cells

Roy, Ananya; Coum, Antoine; Marinescu, Voichita D.; Põlajeva, Jelena; Smits, Anja; Nelander, Sven; Uhrbom, Lene; Westermark, Bengt; Forsberg-Nilsson, Karin; Pontén, Fredrik; Tchougounova, Elena

doi:10.18632/oncotarget.4640

Cited by 34 publications

(29 citation statements)

References 33 publications

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“…proliferative and mesenchymal genes). Interestingly, some of the validated ZBTB18 targets have been previously associated with unfavorable prognosis in glioma [25-27]. Further examination of the top downregulated genes by ZBTB18 in JX6 cells by gene expression array highlighted many genes previously reported to play a role in epithelial-to-mesenchymal transition (EMT) (Figure 3A) [28-34].…”

Section: Resultsmentioning

confidence: 99%

Epigenetic Regulation of ZBTB18 Promotes Glioblastoma Progression

Fedele

Dai

Masilamani

et al. 2017

Molecular Cancer Research

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Glioblastoma (GBM) is comprised of distinct subtypes characterized by their molecular profile. Mesenchymal identity in GBM has been associated with a comparatively unfavorable prognosis, primarily due to inherent resistance of these tumors to current therapies. The identification of molecular determinants of mesenchymal transformation could potentially allow for the discovery of new therapeutic targets. Zinc Finger and BTB Domain Containing 18 (ZBTB18/ZNF238/RP58) is a zinc finger transcriptional repressor with a crucial role in brain development and neuronal differentiation. Here, ZBTB18 is primarily silenced in the mesenchymal subtype of GBM through aberrant promoter methylation. Loss of ZBTB18 contributes to the aggressive phenotype of glioblastoma through regulation of poor prognosis-associated signatures. Restitution of ZBTB18 expression reverses the phenotype and impairs tumor-forming ability. These results indicate that ZBTB18 functions as a tumor suppressor in GBM through the regulation of genes associated with phenotypically aggressive properties. Implications This study characterizes the role of the putative tumor suppressor ZBTB18 and its regulation by promoter hypermethylation, which appears to be a common mechanism to silence ZBTB18 in the mesenchymal subtype of GBM and provides a new mechanistic opportunity to specifically target this tumor subclass.

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Section: Resultsmentioning

confidence: 99%

Epigenetic Regulation of ZBTB18 Promotes Glioblastoma Progression

Fedele

Dai

Masilamani

et al. 2017

Molecular Cancer Research

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“…Seven genes (CSF1, EIF4EBP1, ESM1, IGFBP1, LPL, SERPINE1 and TP53) that were reported to be downregulated by LGI3 may be upregulated in glioma due to the downregulation of LGI3. In particular, CSF1, EIF4EBP1, SERPINE1 and TP53 (p53) were postulated to be functionally involved in glioma 22,30,32,33. Thus, we hypothesize that LGI3 downregulation in glioma may account for downregulation in glioma of the genes that were shown to be upregulated by LGI3 (IGF1 and PTGS2) and upregulation of the genes that were shown to be downregulated by LGI3 (CSF1, EIF4EBP1, ESM1, IGFBP1, LPL, SERPINE1 and TP53).…”

Section: Discussionmentioning

confidence: 96%

Leucine-rich glioma inactivated 3: integrative analyses support its prognostic role in glioma

Kwon¹,

Kim²,

Yun³

2017

OTT

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BackgroundLeucine-rich glioma inactivated 3 (LGI3) is a secreted protein member of LGI family. We previously reported that LGI3 was expressed in brain, adipose tissues and skin, where it played roles as a multifunctional cytokine. We postulated that LGI3 may be involved in cytokine network in cancers.AimThis study aimed to analyze differentially expressed genes in glioma tissues and glioma cohort data to investigate the prognostic role of LGI3 and its receptors.Materials and methodsExpression microarray data from Gene Expression Omnibus and glioma cohort data were analyzed using bioinformatic tools for statistical analysis, protein–protein interactions, functional enrichment and pathway analyses and prognostic association analysis.ResultsWe found that LGI3 and its receptors, ADAM22 and ADAM23, were significantly downregulated in glioma tissues. Eleven upregulated genes and two downregulated genes in glioma tissues were found to be the previously reported LGI3-regulated genes. Protein–protein interaction network analysis showed that 85% of the LGI3-regulated and glioma-altered genes formed a cluster of interaction network. Functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed the association of these genes with hypoxia responses, p53 and Akt signaling and various cancer-related pathways including glioma. Analysis of expression microarray data of glioma cohorts demonstrated that low expression levels of LGI3, ADAM22 and ADAM23 were significantly associated with poor prognosis of glioma.ConclusionThese results propose that LGI3 and its receptors may play a prognostic role in glioma.

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“…Previous investigations have demonstrated that overexpression of SERPINE1 in GBM is associated with shorter survival and its serum levels were shown to be predictive for glioma grade . Roy et al studied the role of SERPINE1 on the mast cells recruitment in gliomas. Deepak suggested heterogeneous activation of TGFβ and increased SERPINE1 expression in GBM .…”

Section: Discussionmentioning

confidence: 99%

NAMPT, GRN, and SERPINE1 signature as predictor of disease progression and survival in gliomas

Vachher

Arora

Burman

et al. 2019

J of Cellular Biochemistry

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Adipose tissue is an important source of adipokines involved in anti‐ and pro‐inflammatory effects. Their involvement in certain cancers such as breast and colon cancer is known but in gliomas it remains unexplored till date. The aim of this study was to assess the status of adipokines as prognostic markers of gliomas (low grade gliomas [LGG] and glioblastoma mutiforme [GBM]). Expression status (messenger RNA [mRNA]), overall survival (OS) and disease‐free survival (DFS) was identified using gene expression profiling interactive analysis server. Clinicopathological analysis and correlation between different adipokines was performed using Xena server. Protein expression status was analyzed using tissue sections from the Human Protein Atlas. Out of 11 adipokines studied visfatin (NAMPT), apelin (APLN), granulin (GRN), serpin peptidase inhibitor/plasminogen activator inhibitor type 1 (PAI‐1) member 1 (SERPINE1), and chemokine (C‐C motif) ligand 2 (CCL2) mRNA levels were significantly upregulated in both LGG and GBM. Interleukin 6 (IL6) mRNA was found be significantly upregulated only in GBM. NAMPT, GRN, SERPINE1, and IL6 showed reduced OS as well as worst DFS for patients having higher mRNA expression in LGG. Increased expression of CCL2 showed worst OS in LGG patients while resistin (RETN) and GRN showed the worst OS in GBM patients. Higher expression of RETN, GRN, IL6, SERPINE1, and CCL2 were found to be positively correlated with shorter DFS in GBM. In the clinicopathological analysis, NAMPT, GRN, IL6, SERPINE1, and CCL2 expressions were significantly associated between the neoplasm histological G2 and G3 grades. Furthermore, expression of NAMPT, GRN, tumor necrosis factor, IL6, SERPINE1, and CCL2 were significantly associated with histological type in LGG patients. NAMPT, GRN, SERPINE1, CCL2, and RETN expression were found to be correlated with each other in gliomas. Finally, NAMPT, GRN, and SERPINE1 were also found to be upregulated using immunohistochemistry in a lower grade and high grade gliomas as compared to normal cells. In conclusion, we have identified key adipokines, namely NAMPT, GRN, and SERPINE1 as potential diagnostic and prognostic markers that might be instrumental in the development and progression of gliomas.

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Glioma-derived plasminogen activator inhibitor-1 (PAI-1) regulates the recruitment of LRP1 positive mast cells

Cited by 34 publications

References 33 publications

Epigenetic Regulation of ZBTB18 Promotes Glioblastoma Progression

Epigenetic Regulation of ZBTB18 Promotes Glioblastoma Progression

Leucine-rich glioma inactivated 3: integrative analyses support its prognostic role in glioma

NAMPT, GRN, and SERPINE1 signature as predictor of disease progression and survival in gliomas

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