Microarray-based Gene Expression Analysis of Melanoma Cell Lines
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE106936 | GEO | 2018/11/30
REPOSITORIES: GEO
Similar Datasets
Project description:Asparagine deprivation by L-Asparaginase is a successful therapeutic strategy in Acute Lymphoblastic Leukemia, with resistance occurring due to upregulation of ASNS. L-Asparaginase efficacy in solid tumors is hampered by dose-related toxicities. Large scale loss of function genetic screens identified ASNS, the only human enzyme synthetizing asparagine, as a cancer dependency in several solid malignancies, including melanoma. We here evaluate the therapeutic potential of targeting ASNS in melanoma cells in-vitro and in-vivo. Using ex-vivo quantitative proteome and transcriptome profiling, we observed that concomitant ASNS deletion and asparagine deprivation elicit a compensatory mechanism allowing tumor growth. Genome wide CRISPR screens upon manipulation of aminoacid levels identifies MAPK and GCN2 as critical nodes mediating the observed resistance mechanism. Importantly MEK and GCN2 inhibitor synergize with L-Asparaginase suggesting novel potential therapeutic strategy in melanoma.
2022-02-15 | PXD015152 | Pride
Project description:Microarray-based Gene Expression Analysis of Melanoma Cell Lines
| PRJNA418465 | ENA
Project description:Cancer progression and therapy resistance arise from metabolic and transcriptional adaptations, but how these are interconnected is less well understood. We propose that in melanoma, the pan-cancer stem cell marker aldehyde dehydrogenase 1A3 (ALDH1A3) couples TFAP2B-neural crest stem cell gene transcription with a distinct acetyl-histone H3 landscape via its substrate acetaldehyde. Mechanistically, nuclear acetyl-CoA synthetase 2 (ACSS2) colocalises with ALDH1A3 to bind glucose metabolic and neural crest stem cell gene loci and promote local acetyl-histone H3 modification dependent on ALDH1A3. Consistent with clinical observations that dedifferentiation into stem cell states confer poor prognosis in melanoma patients and mediate drug resistance, we found in a zebrafish melanoma model that targeting the ALDH1A3-high subpopulation with an ALDH1 suicide inhibitor delayed BRAF inhibitor drug-resistant relapse. Our work identifies ALDH1A3 as a master coordinator of acetaldehyde metabolites that directly regulates chromatin-based gene regulation, and which can be pharmacologically targeted to improve therapeutic outcomes.
2024-06-29 | GSE243834 | GEO
Project description:This experiment uses a transgenic cell line expressing bacterial OGA BtGH84 fused to a localization peptide (NLS) and regulated by Tet-On system. OGA is a glycosidase that removes O-GlcNAc modifications. We evaluated the changes in chromatin openness before and after O-GlcNac removal by OGA.
2024-08-31 | E-MTAB-14350 | biostudies-arrayexpress
Project description:This experiment uses a transgenic cell line expressing bacterial OGA BtGH84 fused to a localization peptide (NLS) and regulated by Tet-On system. OGA is a glycosidase that removes O-GlcNAc modifications. We evaluated the changes in gene expression before and after O-GlcNac removal by OGA.
2024-08-31 | E-MTAB-14311 | biostudies-arrayexpress
Project description:Cancer progression and therapy resistance arise from metabolic and transcriptional adaptations, but how these are interconnected is less well understood. We propose that in melanoma, the pan-cancer stem cell marker aldehyde dehydrogenase 1A3 (ALDH1A3) couples TFAP2B-neural crest stem cell gene transcription with a distinct acetyl-histone H3 landscape via its substrate acetaldehyde. Mechanistically, nuclear acetyl-CoA synthetase 2 (ACSS2) colocalises with ALDH1A3 to bind glucose metabolic and neural crest stem cell gene loci and promote local acetyl-histone H3 modification dependent on ALDH1A3. Consistent with clinical observations that dedifferentiation into stem cell states confer poor prognosis in melanoma patients and mediate drug resistance, we found in a zebrafish melanoma model that targeting the ALDH1A3-high subpopulation with an ALDH1 suicide inhibitor delayed BRAF inhibitor drug-resistant relapse. Our work identifies ALDH1A3 as a master coordinator of acetaldehyde metabolites that directly regulates chromatin-based gene regulation, and which can be pharmacologically targeted to improve therapeutic outcomes.
2024-06-29 | GSE243840 | GEO
Project description:Introduction: Infiltration of cancers by T-cells is associated with improved patient survival and response to immune therapies; however, optimal approaches to induce T-cell infiltration of tumors are not known. This study tests the hypothesis that topical treatment of melanoma metastases with the TLR7 agonist imiquimod treatment plus administration of a multipeptide cancer vaccine will improve immune cell infiltration of melanoma metastases. Patients and Methods: Eligible patients were immunized with a vaccine comprised of 12 melanoma peptides and a tetanus toxoid-derived helper peptide, and imiquimod was applied topically to tumors daily. Adverse events (AE; CTCAE v4.03) were recorded and effects on the tumor microenvironment (TME) were evaluated from sequential tumor biopsies. T-cell responses were assessed by IFNgamma ELIspot assay, and T-cell tetramer staining. Patient tumors were evaluated for immune cell infiltration, cytokine and chemokine production, and gene expression. Results and Conclusions: Four eligible patients were enrolled, and administration of imiquimod and vaccination was well tolerated in these patients. Circulating T-cell responses to the vaccine were detected by ex vivo ELIspot assay in 3 of 4 patients. Treatment of metastases with imiquimod induced immune cell infiltration and favorable gene signatures in the patients with circulating T-cell responses. This study supports further study of topical imiquimod combined with vaccines or other immune therapies for the treatment of melanoma. Precis: This clinical trial tested topical application of imiquimod to melanoma metastases combined with a melanoma vaccine. The regimen dramatically upregulated immune rejection gene signatures in melanoma metastases and increased T-cell infiltrate.
2017-04-01 | GSE80028 | GEO
Project description:To identify improved molecular markers to support histological examination we used microarray analysis of formalin-fixed and paraffin-embedded samples from different stages of melanomagenesis to identify differentially expressed microRNAs. Total RNA were obtained from isolated 19 human cell lines and 52 FFPE human samples. Cells include 2 immortalised melanocytes, 4 ovarian cancer cell lines and 13 melanoma cell lines. 61 FFPE samples include 11 benign naevi, 20 primary and 21 metastatic melanoma
2012-02-08 | E-GEOD-35579 | biostudies-arrayexpress
Project description:This study explored the role of targeting protein for Xklp2 (TPX2), located with 20q11.2, in melanoma pathogenesis, based on initial findings that it was commonly gained and overexpressed. TPX2 copy number was evaluated in melanoma cell lines compared to control DNA. Thrity-three cell lines were analyzed by Agilent SurePrint G3 Human CGH Microarray 2x400K. Samples were compared to Human Female DNA from Promega.
2012-08-27 | E-GEOD-38946 | biostudies-arrayexpress
Project description:The TP53 tumor suppressor is frequently altered in lethal, castration-resistant prostate cancer (CRPC). However, to date there are no effective treatments that specifically target TP53 alterations. Using transcriptomic and metabolomic analyses, we show here that TP53-altered prostate cancer (PCa) exhibits an increased dependency on asparagine and overexpresses asparagine synthetase (ASNS, the enzyme catalyzing the synthesis of asparagine). Mechanistically, loss/mutation of TP53 transcriptionally activate ASNS expression, directly as well as via ATF4, driving de novo asparagine biosynthesis to support CRPC growth. TP53-altered CRPC cells are sensitive to asparagine restriction by knockdown of ASNS and L-asparaginase treatment to deplete the intracellular and extracellular sources of asparagine respectively. This effect was rescued by asparagine addition. Notably, pharmacological inhibition of intracellular asparagine biosynthesis using a glutaminase (GLS) inhibitor and depletion of extracellular asparagine with L-asparaginase significantly reduced asparagine production and effectively impaired CRPC growth. This study highlights the significance of ASNS-mediated metabolic adaptation as a synthetic vulnerability in CRPC with TP53 alterations, providing a rationale for co-targeting intracellular and extracellular asparagine production to treat these lethal prostate cancers.
2024-02-29 | GSE255000 | GEO