Expression of dual angiogenic/neurogenic growth factors in human primary brain tumors

Clemessy, Maud; Janzer, Robert C.; Lhermitte, Benoît; Gasc, Jean‐Marie; Juillerat‐Jeanneret, Lucienne

doi:10.1007/s11060-011-0715-1

Cited by 7 publications

(5 citation statements)

References 26 publications

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“…Reduced transcript availability for the TGF-beta type I receptor, which likely results in compromised TGF-beta signaling, is accompanied by a decrease in transcripts for Wnt10b (axonal guidance [44], [45]) coupled with increased (p = 0.039) transcript availability for Gas2L1 (expressed at high levels in growth arrested cells). The Hltf null brain phenotype is further characterized by decreased transcripts (Table S3) for Ska2 mRNA (mitotic arrest [46]); Tnik (neuritogenesis [47]); and Bmp5 and Bambi (neural development [48]). …”

Section: Resultsmentioning

confidence: 99%

Role of Helicase-Like Transcription Factor (Hltf) in the G2/M Transition and Apoptosis in Brain

Helmer

Foreman²,

Dertien

et al. 2013

PLoS ONE

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HLTF participates in transcription, chromatin remodeling, DNA damage repair, and tumor suppression. Aside from being expressed in mouse brain during embryonic and postnatal development, little is known about Hltf's functional importance. Splice variant quantification of wild-type neonatal (6-8 hour postpartum) brain gave a ratio of 5:1 for Hltf isoform 1 (exons 1-25) to isoform 2 (exons 1-21 with exon 21 extended via a partial intron retention event). Western analysis showed a close correlation between mRNA and protein expression. Complete loss of Hltf caused encephalomalacia with increased apoptosis, and reduced viability. Sixty-four percent of Hltf null mice died, 48% within 12-24 hours of birth. An RNA-Seq snapshot of the neonatal brain transcriptome showed 341 of 20,000 transcripts were altered (p < 0.05) - 95 up regulated and 246 down regulated. MetaCoreTM enrichment pathway analysis revealed Hltf regulates cell cycle, cell adhesion, and TGF-beta receptor signaling. Hltf's most important role is in the G2/M transition of the cell cycle (p = 4.672e-7) with an emphasis on transcript availability of major components in chromosome cohesion and condensation. Hltf null brains have reduced transcript levels for Rad21/Scc1, histone H3.3, Cap-E/Smc2, Cap-G/G2, and Aurora B kinase. The loss of Hltf in its yeast Rad5-like role in DNA damage repair is accompanied by down regulation of Cflar, a critical inhibitor of TNFRSF6-mediated apoptosis, and increased (p<0.0001) active caspase-3, an indicator of intrinsic triggering of apoptosis in null brains. Hltf also regulates Smad7/Bambi/Tgf-beta/Bmp5/Wnt10b signaling in brain. ChIP confirmed Hltf binding to consensus sequences in predicted (promoter Scgb3a1 gene) and previously unidentified (P-element on chromosome 7) targets. This study is the first to provide a comprehensive view of Hltf targets in brain. Moreover, it reveals how silencing Hltf disrupts cell cycle progression, and attenuates DNA damage repair.

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Section: Resultsmentioning

confidence: 99%

Role of Helicase-Like Transcription Factor (Hltf) in the G2/M Transition and Apoptosis in Brain

Helmer

Foreman²,

Dertien

et al. 2013

PLoS ONE

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“…The inhibition of methyltransferases that are functionally or structurally related to METTL17 rescued synaptic and cognitive functions for Alzheimer’s disease [ 106 ]. The RHOGEF Neuroepithelial cell-transforming 1 (NET1) is involved in cell proliferation in neurological development [ 107 ]. The basic helix-loop-helix (bHLH) transcription factor Neurogenin 2 (NEUROG2) plays a role in the development of Neurons via the Wnt/β-Catenin pathway [ 108 ].…”

Section: Discussionmentioning

confidence: 99%

The plasma peptides of Alzheimer’s disease

Florentinus-Mefailoski

Bowden

Scheltens

et al. 2021

Clin Proteom

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Background A practical strategy to discover proteins specific to Alzheimer’s dementia (AD) may be to compare the plasma peptides and proteins from patients with dementia to normal controls and patients with neurological conditions like multiple sclerosis or other diseases. The aim was a proof of principle for a method to discover proteins and/or peptides of plasma that show greater observation frequency and/or precursor intensity in AD. The endogenous tryptic peptides of Alzheimer’s were compared to normals, multiple sclerosis, ovarian cancer, breast cancer, female normal, sepsis, ICU Control, heart attack, along with their institution-matched controls, and normal samples collected directly onto ice. Methods Endogenous tryptic peptides were extracted from blinded, individual AD and control EDTA plasma samples in a step gradient of acetonitrile for random and independent sampling by LC–ESI–MS/MS with a set of robust and sensitive linear quadrupole ion traps. The MS/MS spectra were fit to fully tryptic peptides within proteins identified using the X!TANDEM algorithm. Observation frequency of the identified proteins was counted using SEQUEST algorithm. The proteins with apparently increased observation frequency in AD versus AD Control were revealed graphically and subsequently tested by Chi Square analysis. The proteins specific to AD plasma by Chi Square with FDR correction were analyzed by the STRING algorithm. The average protein or peptide log10 precursor intensity was compared across disease and control treatments by ANOVA in the R statistical system. Results Peptides and/or phosphopeptides of common plasma proteins such as complement C2, C7, and C1QBP among others showed increased observation frequency by Chi Square and/or precursor intensity in AD. Cellular gene symbols with large Chi Square values (χ2 ≥ 25, p ≤ 0.001) from tryptic peptides included KIF12, DISC1, OR8B12, ZC3H12A, TNF, TBC1D8B, GALNT3, EME2, CD1B, BAG1, CPSF2, MMP15, DNAJC2, PHACTR4, OR8B3, GCK, EXOSC7, HMGA1 and NT5C3A among others. Similarly, increased frequency of tryptic phosphopeptides were observed from MOK, SMIM19, NXNL1, SLC24A2, Nbla10317, AHRR, C10orf90, MAEA, SRSF8, TBATA, TNIK, UBE2G1, PDE4C, PCGF2, KIR3DP1, TJP2, CPNE8, and NGF amongst others. STRING analysis showed an increase in cytoplasmic proteins and proteins associated with alternate splicing, exocytosis of luminal proteins, and proteins involved in the regulation of the cell cycle, mitochondrial functions or metabolism and apoptosis. Increases in mean precursor intensity of peptides from common plasma proteins such as DISC1, EXOSC5, UBE2G1, SMIM19, NXNL1, PANO, EIF4G1, KIR3DP1, MED25, MGRN1, OR8B3, MGC24039, POLR1A, SYTL4, RNF111, IREB2, ANKMY2, SGKL, SLC25A5, CHMP3 among others were associated with AD. Tryptic peptides from the highly conserved C-terminus of DISC1 within the sequence MPGGGPQGAPAAAGGGGVSHRAGSRDCLPPAACFR and ARQCGLDSR showed a higher frequency and highest intensity in AD compared to all other disease and controls. Conclusion Proteins apparently expressed in the brain that were directly related to Alzheimer’s including Nerve Growth Factor (NFG), Sphingomyelin Phosphodiesterase, Disrupted in Schizophrenia 1 (DISC1), the cell death regulator retinitis pigmentosa (NXNl1) that governs the loss of nerve cells in the retina and the cell death regulator ZC3H12A showed much higher observation frequency in AD plasma vs the matched control. There was a striking agreement between the proteins known to be mutated or dis-regulated in the brains of AD patients with the proteins observed in the plasma of AD patients from endogenous peptides including NBN, BAG1, NOX1, PDCD5, SGK3, UBE2G1, SMPD3 neuronal proteins associated with synapse function such as KSYTL4, VTI1B and brain specific proteins such as TBATA.

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“…Several studies have highlighted the link between NRPs and tumor progression in different cancer types, notably in brain cancers. More precisely, NRP1 was expressed in different cerebral tumors at a relatively high level of expression, no matter the type or the grade of the tumor ( Figure 2 ), while the expression of NRP2 seems to be constantly low in all brain tumors ( 73 , 74 ), demonstrating that its presence alone is correlated with poor prognosis ( 75 ). Thus, NRPs have been shown to play an important role in tumorigenesis, tumor development, tumor invasion, and tumor angiogenesis in adult brain tumors.…”

Section: Neuropilin-1mentioning

confidence: 98%

Neuropilin-1: A Key Protein to Consider in the Progression of Pediatric Brain Tumors

2021

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Neuropilins are transmembrane glycoproteins that play important roles in cardiovascular and neuronal development, as well as in immunological system regulations. NRP1 functions as a co-receptor, binding numerous ligands, such as SEMA 3 or VEGF and, by doing so, reinforcing their signaling pathways and can also interface with the cytoplasmic protein synectin. NRP1 is expressed in many cancers, such as brain cancers, and is associated with poor prognosis. The challenge today for patients with pediatric brain tumors is to improve their survival rate while minimizing the toxicity of current treatments. The aim of this review is to highlight the involvement of NRP1 in pediatric brain cancers, focusing essentially on the roles of NRP1 in cancer stem cells and in the regulation of the immune system. For this purpose, recent literature and tumor databases were analyzed to show correlations between NRP1 and CD15 (a stem cancer cells marker), and between NRP1 and PDL1, for various pediatric brain tumors, such as high- and low-grade gliomas, medulloblastomas, and ependymomas. Finally, this review suggests a relevant role for NRP1 in pediatric brain tumors progression and identifies it as a potential diagnostic or therapeutic target to improve survival and life quality of these young patients.

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Expression of dual angiogenic/neurogenic growth factors in human primary brain tumors

Cited by 7 publications

References 26 publications

Role of Helicase-Like Transcription Factor (Hltf) in the G2/M Transition and Apoptosis in Brain

Role of Helicase-Like Transcription Factor (Hltf) in the G2/M Transition and Apoptosis in Brain

The plasma peptides of Alzheimer’s disease

Neuropilin-1: A Key Protein to Consider in the Progression of Pediatric Brain Tumors

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