Glutaredoxin 2 promotes SP-1-dependent CSPG4 transcription and migration of wound healing NG2 glia and glioma cells: Enzymatic Taoism

Wilms, Christina; Lepka, Klaudia; Häberlein, Felix; Edwards, Steven J; Felsberg, Jög; Pudelko, Linda; Lindenberg, Tobias; Poschmann, Gereon; Qin, Nan; Volbracht, Katrin; Prozorovski, Timour; Meuth, Sven G.; Kahlert, Ulf D.; Remke, Marc; Aktaş, Orhan; Reifenberger, Guido; Bräutigam, Lars; Odermatt, Benjamin; Berndt, Carsten

doi:10.1016/j.redox.2021.102221

Cited by 9 publications

(9 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This activation also promotes the EMT process and the expression of VM related genes genes. Additionally, prior studies also report that CSPG4 may foster proliferation, migration, and invasion of tumor cells by regulating EMT-related pathways ( Winship et al, 2017 ; Wilms et al, 2022 ). To sum up, CAFs promote VM formation through multiple pathways including fibronectin and laminin as well as potentially key mechanisms such as HGF/MET and CSPG4 pathways.…”

Section: Discussionmentioning

confidence: 97%

Pan-cancer dissection of vasculogenic mimicry characteristic to provide potential therapeutic targets

Tang,

Chen,

Liu

et al. 2024

Front. Pharmacol.

View full text Add to dashboard Cite

Introduction:Vasculogenic mimicry (VM) represents a novel form of tumor angiogenesis that is associated with tumor invasiveness and drug resistance. However, the VM landscape across cancer types remains poorly understood. In this study, we elucidate the characterizations of VM across cancers based on multi-omics data and provide potential targeted therapeutic strategies.Methods:Multi-omics data from The Cancer Genome Atlas was used to conduct comprehensive analyses of the characteristics of VM related genes (VRGs) across cancer types. Pan-cancer vasculogenic mimicry score was established to provide a depiction of the VM landscape across cancer types. The correlation between VM and cancer phenotypes was conducted to explore potential regulatory mechanisms of VM. We further systematically examined the relationship between VM and both tumor immunity and tumor microenvironment (TME). In addition, cell communication analysis based on single-cell transcriptome data was used to investigate the interactions between VM cells and TME. Finally, transcriptional and drug response data from the Genomics of Drug Sensitivity in Cancer database were utilized to identify potential therapeutic targets and drugs. The impact of VM on immunotherapy was also further clarified.Results:Our study revealed that VRGs were dysregulated in tumor and regulated by multiple mechanisms. Then, VM level was found to be heterogeneous among different tumors and correlated with tumor invasiveness, metastatic potential, malignancy, and prognosis. VM was found to be strongly associated with epithelial-mesenchymal transition (EMT). Further analyses revealed cancer-associated fibroblasts can promote EMT and VM formation. Furthermore, the immune-suppressive state is associated with a microenvironment characterized by high levels of VM. VM score can be used as an indicator to predict the effect of immunotherapy. Finally, seven potential drugs targeting VM were identified.Conclusion:In conclusion, we elucidate the characteristics and key regulatory mechanisms of VM across various cancer types, underscoring the pivotal role of CAFs in VM. VM was further found to be associated with the immunosuppressive TME. We also provide clues for the research of drugs targeting VM. Our study provides an initial overview and reference point for future research on VM, opening up new avenues for therapeutic intervention.

show abstract

Section: Discussionmentioning

confidence: 97%

Pan-cancer dissection of vasculogenic mimicry characteristic to provide potential therapeutic targets

Tang,

Chen,

Liu

et al. 2024

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…Enzymatically active apo-Grx2 is required, for instance, for brain and vascular development (Bräutigam et al , 2011, 2013), and promotes cell migration of cancer cells (Gellert et al , 2020; Wilms et al , 2022). The same mode of cluster coordination was also demonstrated for the human monothiol Grxs 3 and 5 (Haunhorst et al , 2010; Johansson et al , 2011) that function in iron homeostasis and FeS cluster biosynthesis, as well as for various Grxs from other species, for overviews see for instance (Berndt & Lillig, 2017; Rouhier et al , 2010).…”

Section: Discussionmentioning

confidence: 99%

FeS-cluster coordination of vertebrate thioredoxin regulates suppression of hypoxia-induced factor 2α through iron regulatory protein 1

Berndt

Hanschmann

Urbainsky³

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Thioredoxins (Trxs) provide electrons to essential cellular processes such as DNA synthesis. Here, we characterize human and murine Trx1 as new iron-sulfur proteins. The [2Fe-2S] cluster is complexed using cysteinyl side chains 32 and 73 in a dimeric holocomplex. Formation of the holo-dimer depends on small structural changes of the loop connecting helices three and four and is stabilized by the formation of a direct electrostatic interaction between Lys72 and Asp60 of two monomers. The not strictly conserved Cys73 in vertebrates co-evolved with the regulation of cellular iron homeostasis through the iron-regulatory proteins (IRP). Active apo-Trx1 is required for the reduction of cysteinyl residues in IRP1 and its binding to the iron-responsive elements in the mRNA encoding hypoxiainducible factor (HIF) 2α. Depletion of Trx1 increased the mRNA levels of HIF2α, an important target of IRP1. Hence, translation of the HIF2α mRNA requires either sufficient iron-supply or the lack of reducing power of the Trx system under iron-limiting conditions. Only then, HIF2α protein may accumulate under hypoxic conditions to transcriptionally regulate processes like erythropoiesis.Significance StatementThioredoxins are, in general, cofactor-less key proteins in redox regulation and provide electrons to many essential cellular processes such as DNA synthesis. 55 years after its discovery, we show that mammalian thioredoxin 1 coordinates an iron-sulfur cluster using one of its active site cysteinyl residues and a non-conserved additional cysteinyl residue located outside the active site. This particular residue co-evolved with the vertebratespecific iron regulatory system. Our study demonstrates that this system is regulated by thioredoxin 1 at the level of the iron-regulatory protein 1, thus linking redox and iron homeostases.

show abstract

“…Moreover, the co-employment of irf8 −/− mutants lacking microglia can be useful in further investigating their the role in GBM progression and survival [140]. Zebrafish neural stem cells, astrocytes, and oligodendrocytes have also been defined by marking, respectively, the glial fibrillary acid protein (gfap) in Tg (gfap:GFP) [106] and oligodendrocyte transcription factor 2 (olig2) in Tg (olig2:GPF) [141] lines.…”

Section: Transgenic and Transplantation (Xenograft) Zebrafish Modelsmentioning

confidence: 99%

Speeding up Glioblastoma Cancer Research: Highlighting the Zebrafish Xenograft Model

Alberti,

Amico,

Caruso Bavisotto

et al. 2024

IJMS

View full text Add to dashboard Cite

Glioblastoma multiforme (GBM) is a very aggressive and lethal primary brain cancer in adults. The multifaceted nature of GBM pathogenesis, rising from complex interactions between cells and the tumor microenvironment (TME), has posed great treatment challenges. Despite significant scientific efforts, the prognosis for GBM remains very poor, even after intensive treatment with surgery, radiation, and chemotherapy. Efficient GBM management still requires the invention of innovative treatment strategies. There is a strong necessity to complete cancer in vitro studies and in vivo studies to properly evaluate the mechanisms of tumor progression within the complex TME. In recent years, the animal models used to study GBM tumors have evolved, achieving highly invasive GBM models able to provide key information on the molecular mechanisms of GBM onset. At present, the most commonly used animal models in GBM research are represented by mammalian models, such as mouse and canine ones. However, the latter present several limitations, such as high cost and time-consuming management, making them inappropriate for large-scale anticancer drug evaluation. In recent years, the zebrafish (Danio rerio) model has emerged as a valuable tool for studying GBM. It has shown great promise in preclinical studies due to numerous advantages, such as its small size, its ability to generate a large cohort of genetically identical offspring, and its rapid development, permitting more time- and cost-effective management and high-throughput drug screening when compared to mammalian models. Moreover, due to its transparent nature in early developmental stages and genetic and anatomical similarities with humans, it allows for translatable brain cancer research and related genetic screening and drug discovery. For this reason, the aim of the present review is to highlight the potential of relevant transgenic and xenograft zebrafish models and to compare them to the traditionally used animal models in GBM research.

show abstract

Glutaredoxin 2 promotes SP-1-dependent CSPG4 transcription and migration of wound healing NG2 glia and glioma cells: Enzymatic Taoism

Cited by 9 publications

References 60 publications

Pan-cancer dissection of vasculogenic mimicry characteristic to provide potential therapeutic targets

Pan-cancer dissection of vasculogenic mimicry characteristic to provide potential therapeutic targets

FeS-cluster coordination of vertebrate thioredoxin regulates suppression of hypoxia-induced factor 2α through iron regulatory protein 1

Speeding up Glioblastoma Cancer Research: Highlighting the Zebrafish Xenograft Model

Contact Info

Product

Resources

About