Homo sapiens
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PROVIDER: PRJNA338981 | ENA |
REPOSITORIES: ENA
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Project description:Epigenetic Activation of WNT5A Drives Glioblastoma Stem Cell Differentiation and Invasive Growth [ChIP-Seq]
| PRJNA342432 | ENA
Project description:Chromatin and transcriptome comparisons of matched NSCs and derivative GSCs reveal activation of WNT5A and an EC signature WNT5A-mediated GdEC differentiation and EC recruitment support the invasive growth of glioma cells in the brain parenchyma.
2016-12-17 | GSE85615 | GEO
Project description:Wnt5a Drives The State Transition To An Invasive Phenotype In Human Glioblastoma Cancer Stem Cells
| PRJNA307251 | ENA
Project description:We have previously shown that Wnt5A drives invasion in melanoma. We have also shown that Wnt5A promotes resistance to therapy designed to target the BRAF(V600E) mutation in melanoma. Here, we show that melanomas characterized by high levels of Wnt5A respond to therapeutic stress by increasing p21 and expressing classical markers of senescence, including positivity for senescence-associated ?-galactosidase (SA-?-gal), senescence-associated heterochromatic foci (SAHF), H3K9Me chromatin marks, and PML bodies. We find that despite this, these cells retain their ability to migrate and invade. Further, despite the expression of classic markers of senescence such as SA-?-gal and SAHF, these Wnt5A-high cells are able to colonize the lungs in in vivo tail vein colony-forming assays. This clearly underscores the fact that these markers do not indicate true senescence in these cells, but instead an adaptive stress response that allows the cells to evade therapy and invade. Notably, silencing Wnt5A reduces expression of these markers and decreases invasiveness. The combined data point to Wnt5A as a master regulator of an adaptive stress response in melanoma, which may contribute to therapy resistance. To better understand the molecular mechanisms governing the response of highly invasive cells to IR as compared to that of poorly invasive cells, we performed microarray analysis of both poorly and highly invasive cells at early and late timepoints after irradiation. Cells were treated with y-irradiation, and RNA was taken at 1 hour, 24 hours and 5 days after irradiation. Microarray analysis was performed using Illumina Human HT-12 ver3 expression arrays, and each time point was compared to RNA from untreated cells.
2015-08-07 | E-GEOD-50004 | biostudies-arrayexpress
Project description:Glioblastoma (GBM), classified as a grade 4 glioma, is the most prevalent intrinsic malignancy of the central nervous system. Glioblastoma stem cells (GSCs) are small populations of GBM cells with self-renewal and multilineage differentiation capabilities and are considered responsible for the tumorigenesis and development of GBM. GSCs also exhibit radiation resistance, chemoresistance, and angiogenic and invasive properties, which are correlated with poor outcomes in GBM patients. Therefore, targeting GSCs constitutes a promising approach for treating GBM patients. Our findings revealed that POSTN secreted from GSCs promotes GSC self-renewal and tumor growth via activation of the αVβ3/PI3K/AKT/β-catenin/FOSL1 pathway.
2024-08-01 | GSE273252 | GEO
Project description:Glioblastoma (GBM), classified as a grade 4 glioma, is the most prevalent intrinsic malignancy of the central nervous system. Glioblastoma stem cells (GSCs) are small populations of GBM cells with self-renewal and multilineage differentiation capabilities and are considered responsible for the tumorigenesis and development of GBM. GSCs also exhibit radiation resistance, chemoresistance, and angiogenic and invasive properties, which are correlated with poor outcomes in GBM patients. Therefore, targeting GSCs constitutes a promising approach for treating GBM patients. Our findings revealed that POSTN secreted from GSCs promotes GSC self-renewal and tumor growth via activation of the αVβ3/PI3K/AKT/β-catenin/FOSL1 pathway.
2024-08-01 | GSE273250 | GEO
Project description:<p>Glioblastoma (GBM) is a common and deadly form of brain tumor in adults. Dysregulated metabolism in GBM offers an opportunity to deploy metabolic interventions as precise therapeutic strategies. To identify the molecular drivers and the modalities by which different molecular subgroups of GBM exploit metabolic rewiring to sustain tumor progression, we interrogated the transcriptome, the metabolome, and the glycoproteome of human subgroup-specific GBM sphere-forming cells (GSC). L-fucose abundance and core fucosylation activation were elevated in mesenchymal (MES) compared with proneural GSCs; this pattern was retained in subgroup-specific xenografts and in subgroup-affiliated human patient samples. Genetic and pharmacological inhibition of core fucosylation significantly reduced tumor growth in MES GBM preclinical models. Liquid chromatography-mass spectrometry (LC-MS)-based glycoproteomic screening indicated that most MES-restricted core-fucosylated proteins are involved in therapeutically relevant GBM pathological processes, such as extracellular matrix interaction, cell adhesion, and integrin-mediated signaling. Selective L-fucose accumulation in MES GBMs was observed using preclinical minimally invasive PET, implicating this metabolite as a potential subgroup-restricted biomarker.Overall, these findings indicate that L-fucose pathway activation in MES GBM is a subgroup-specific dependency that could provide diagnostic markers and actionable therapeutic targets.</p><h4><strong>SIGNIFICANCE: </strong>Metabolic characterization of subgroup-specific glioblastoma (GBM) sphere-forming cells identifies the L-fucose pathway as a vulnerability restricted to mesenchymal GBM, disclosing a potential precision medicine strategy for targeting cancer metabolism.</h4><p><br></p><p><strong>Stem cell and cell line assays</strong> are reported in the current study <a href='https://www.ebi.ac.uk/metabolights/MTBLS4708' rel='noopener noreferrer' target='_blank'><strong>MTBLS4708</strong></a>.</p><p><strong>Xenograft assays</strong> are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS730' rel='noopener noreferrer' target='_blank'><strong>MTBLS730</strong></a>.</p>
2022-11-08 | MTBLS4708 | MetaboLights
Project description:<p>Glioblastoma (GBM) is a common and deadly form of brain tumor in adults. Dysregulated metabolism in GBM offers an opportunity to deploy metabolic interventions as precise therapeutic strategies. To identify the molecular drivers and the modalities by which different molecular subgroups of GBM exploit metabolic rewiring to sustain tumor progression, we interrogated the transcriptome, the metabolome, and the glycoproteome of human subgroup-specific GBM sphere-forming cells (GSC). L-fucose abundance and core fucosylation activation were elevated in mesenchymal (MES) compared with proneural GSCs; this pattern was retained in subgroup-specific xenografts and in subgroup-affiliated human patient samples. Genetic and pharmacological inhibition of core fucosylation significantly reduced tumor growth in MES GBM preclinical models. Liquid chromatography-mass spectrometry (LC-MS)-based glycoproteomic screening indicated that most MES-restricted core-fucosylated proteins are involved in therapeutically relevant GBM pathological processes, such as extracellular matrix interaction, cell adhesion, and integrin-mediated signaling. Selective L-fucose accumulation in MES GBMs was observed using preclinical minimally invasive PET, implicating this metabolite as a potential subgroup-restricted biomarker.Overall, these findings indicate that L-fucose pathway activation in MES GBM is a subgroup-specific dependency that could provide diagnostic markers and actionable therapeutic targets.</p><h4><strong>SIGNIFICANCE: </strong>Metabolic characterization of subgroup-specific glioblastoma (GBM) sphere-forming cells identifies the L-fucose pathway as a vulnerability restricted to mesenchymal GBM, disclosing a potential precision medicine strategy for targeting cancer metabolism.</h4><p><br></p><p><strong>Xenograft assays</strong> are reported in the current study <strong>MTBLS730</strong>.</p><p><strong>Stem cell and cell line assays</strong> are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS4708' rel='noopener noreferrer' target='_blank'><strong>MTBLS4708</strong></a>.</p>
2022-11-08 | MTBLS730 | MetaboLights
Project description:About half of all melanomas harbor a constitutively active mutant BRAFV600E/K kinase that can be selectively inhibited by targeted BRAF inhibitors (BRAFi). While patients treated with BRAFi initially exhibit measurable clinical improvement, the majority of patients eventually develop drug resistance and relapse. We observe significant elevation of WNT5A in a subset of tumors from patients exhibiting disease progression on BRAFi therapy. WNT5A transcript and protein are also elevated in BRAFi-resistant melanoma cell lines generated by long-term in vitro treatment with BRAFi. RNAi-mediated reduction in levels of endogenous WNT5A in melanoma decreases cell growth, increases apoptosis in response to BRAFi challenge, and decreases the activity of pro-survival AKT signaling. Overexpression of WNT5A conversely promotes melanoma growth and tumorigenesis and activates AKT signaling. Similar to WNT5A knockdown, knockdown of the WNT receptors FZD7 and RYK inhibits growth, sensitizes melanoma cells to BRAFi, and reduces AKT activation. Together, these findings suggest that chronic BRAF inhibition elevates WNT5A expression, which then acts through FZD7 and RYK to promote AKT signaling, leading to increased growth and therapeutic resistance. Increased WNT5A expression in BRAFi-resistant melanomas also correlates with an associated transcriptional signature, which identifies potential therapeutic targets to reduce clinical resistance to BRAFi. Expression of WNT5A-correlated genes was compared in melanoma cell lines generated to be resistant to PLX4032 and the their associated naïve parental line Basal expression of the WNT5A-correlated genes was also measured in experiments comparing each naïve line to a mixed reference pool containing equal amounts of 47 melanoma cell lines.
2014-03-06 | E-GEOD-55583 | biostudies-arrayexpress
Project description:Ror2 is a member of the Ror-family of receptor tyrosine kinases acting as a receptor for Wnt5a. Wnt5a/Ror2 signaling activates primarily the ß-catenin-independent pathway, which involves various signal mediators, such as Dishevelled, c-Jun N-terminal kinase (JNK), filamin A, c-Src, and Ca2+. Wnt5a/Ror2 signaling has also been shown to inhibit the ß-catenin-dependent pathway. Wnt5a and Ror2 are overexpressed in various types of tumor cells, including osteosarcoma and melanoma cells, resulting in constitutive activation of Wnt5a/Ror2 signaling in a cell-autonomous manner. Constitutively activated Wnt5a/Ror2 signaling has been shown to play important roles in promoting invadopodia formation and invasiveness of tumor cells. However, little is known about the mechanisms underlying these processes. As an attempt to understand the mechanism by which Wnt5a/Ror2 signaling, activated constitutively in osteosarcoma cells, contributes to their highly invasive properties, we performed DNA microarray analysis using a human osteosarcoma cell line, SaOS2.
2017-01-01 | GSE76535 | GEO