Cellular fitness of MYC-driven cancer cells to genetic and pharmacologic perturbations in normoxia, hypoxia and 3D
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PROVIDER: PRJNA1090128 | ENA |
REPOSITORIES: ENA
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Project description:Cellular fitness of MYC-driven cancer cells to genetic and pharmacologic perturbations in normoxia, hypoxia and 3D
| PRJNA1005987 | ENA
Project description:MYC and hypoxia gene clusters are the two most commonly recurring transcriptional programs in heterogenous tumors. Understanding the cellular fitness of MYC-driven cancer cells in normoxia and hypoxia may lead to identification of distinct cancer cell vulnerabilities. Using genome-wide CRISPR screenings of MYC-driven liver cancer cells cultured over 4 weeks in 21% and 1% oxygen in monolayer, and 21% oxygen in 3D spheroid, we not only identify over 600 essential genes under all three conditions but also context-specific fitness genes and pathways. Knockout of VHL-HIF1 pathway results in incompatible fitness defects under 21% oxygen versus 1% oxygen or 3D. Genetic deletion of each of the mitochondrial respiratory complex I-V has distinct cellular fitness outcomes. Notably, the organogenesis signaling pathways such as TGF-SMAD specifically limits the uncontrolled cell proliferation of 3D spheroids while inactivation of epigenetic modifiers (Bcor, Kmt2d, Mettl3 and Mettl14) has opposite outcomes in monolayer versus 3D. We also discover distinct metabolic requirement for fatty acid and cholesterol synthesis in three conditions. Chemical perturbations using 125 FDA approved oncology drugs reveal that MYC-driven liver cancer cells have different sensitivity to inhibition of tyrosine kinase receptors under hypoxia and 3D. Our resource study highlights unique epigenetic and metabolic dependency of MYC-driven cancer cells in different tumor environmental settings.
2024-06-26 | GSE240980 | GEO
Project description:MYC and hypoxia gene clusters are the two most commonly recurring transcriptional programs in heterogenous tumors. Understanding the cellular fitness of MYC-driven cancer cells in normoxia and hypoxia may lead to identification of distinct cancer cell vulnerabilities. Using genome-wide CRISPR screenings of MYC-driven liver cancer cells cultured over 4 weeks in 21% and 1% oxygen in monolayer, and 21% oxygen in 3D spheroid, we not only identify over 600 essential genes under all three conditions but also context-specific fitness genes and pathways. Knockout of VHL-HIF1 pathway results in incompatible fitness defects under 21% oxygen versus 1% oxygen or 3D. Genetic deletion of each of the mitochondrial respiratory complex I-V has distinct cellular fitness outcomes. Notably, the organogenesis signaling pathways such as TGF-SMAD specifically limits the uncontrolled cell proliferation of 3D spheroids while inactivation of epigenetic modifiers (Bcor, Kmt2d, Mettl3 and Mettl14) has opposite outcomes in monolayer versus 3D. We also discover distinct metabolic requirement for fatty acid and cholesterol synthesis in three conditions. Chemical perturbations using 125 FDA approved oncology drugs reveal that MYC-driven liver cancer cells have different sensitivity to inhibition of tyrosine kinase receptors under hypoxia and 3D. Our resource study highlights unique epigenetic and metabolic dependency of MYC-driven cancer cells in different tumor environmental settings.
2024-06-26 | GSE262074 | GEO
Project description:Estrogen receptor alpha plays a critical role in breast cancer and is a major target in endocrine therapy. HIF-1 alpha have been associated with ER alpha and predict a worse outcome. Recent studies indicate that histone demethylase JMJD2B is a HIF-1 alpha target. However, little is known about the biological functions of JMJD2B, especially in breast cancer. To elucidate the mechanism by which JMJD2B reguates gene expression in normoxia and hypoxia, MCF-7 breast cancer cells were depleted forJMJD2B in normoxia and hypoxia. Our results provide insight into JMJD2B regulation of gene expression in breast cancer cells in normoxia and hypoxia.
2010-09-01 | GSE18384 | GEO
Project description:Estrogen receptor alpha plays a critical role in breast cancer and is a major target in endocrine therapy. HIF-1 alpha have been associated with ER alpha and predict a worse outcome. Recent studies indicate that histone demethylase JMJD2B is a HIF-1 alpha target. However, little is known about the biological functions of JMJD2B, especially in breast cancer. To elucidate the mechanism by which JMJD2B reguates gene expression in normoxia and hypoxia, MCF-7 breast cancer cells were depleted forJMJD2B in normoxia and hypoxia. Our results provide insight into JMJD2B regulation of gene expression in breast cancer cells in normoxia and hypoxia. MCF7 cells were subjected to transfection with siRNA controls and two different siRNA oligos against JMJD2B for 24 hours. Cells were treated in normoxia and hypoxia for another 16 hours.
2010-09-01 | E-GEOD-18384 | biostudies-arrayexpress
Project description:Extracellular vesicles (EVs) represent a diverse group of small membrane-encapsulated particles and provide a universal molecular cell-cell communication system. Hypoxia is a typical condition in solid tumors, and cancer-derived EVs support growth and invasion of tissues by tumor cells. EVs were purified from cell culture medium by ultracentrifugation followed by size exclusion chromatography with Exo-spin™ columns (Cell Guidance Systems Ltd). We performed proteomic analysis of five hypoxia/normoxia pairs of EV samples; each of these replicates for either hypoxia or normoxia was analyzed in duplicates. Obtained data were compared with proteomics analysis of corresponding cell culture media supernatants (SN) after EV removal with 100 000 g ultracentrifugation. We found that exposure of tumor cells to hypoxia (1% oxygen) induced EV secretion, altered EV sizes, and led to notable changes in the EV protein cargo in comparison to normoxia.
2022-02-16 | PXD023546 | Pride
Project description:Lysates of Mycobacterium tuberculosis (H37Rv auxotroph mc(2)6020) grown under various conditions (normoxia, hypoxia, reactivation from hypoxia) probed the serine hydrolase probe with ActivX-desthiobiotin FP.
2016-10-10 | MSV000080238 | MassIVE
Project description:We used miRNA array to study differential expression of miRNA under hypoxia exposure in cancer cells. Cells cultured under normoxia were used as controls.
2016-10-20 | GSE52743 | GEO
Project description:<p>The gut microbiota operates at the interface of host-environment interactions to influence human homeostasis and metabolic networks. Environmental factors that unbalance gut microbial ecosystems can therefore elicit physiological and disease-associated responses across somatic tissues. However, the systemic impact of the gut microbiome on the germline - and consequently on the F1 offspring it gives rise to - is unexplored. Here we show that the gut microbiota act as a key interface between paternal preconception environment and intergenerational health in mice. Perturbations to the gut microbiota of prospective fathers increase the probability of their offspring presenting with low birth weight, severe growth restriction and premature mortality. Transmission of disease risk occurs via the germline and is provoked by pervasive gut microbiome perturbations, including non-absorbable antibiotics or osmotic laxatives, but is rescued by restoring the paternal microbiota before conception. This effect is linked with a dynamic response to induced dysbiosis in the male reproductive system, including impaired leptin signalling, altered testicular metabolite profiles and remapped small RNA payloads in sperm. As a result, dysbiotic fathers trigger an elevated risk of in utero placental insufficiency, revealing a placental origin of mammalian intergenerational effects. Our study defines a regulatory ‘gut-germline axis’ in males, which is sensitive to environmental exposures and programs offspring fitness through impacting placental function.</p>
2024-02-12 | MTBLS1629 | MetaboLights
Project description:Paternal microbiome perturbations impact offspring fitness in mice.
| PRJEB43500 | ENA