Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA363001 | ENA |
REPOSITORIES: ENA
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Project description:The conditions of the tumor microenvironment, such as hypoxia and nutrient starvation, play critical roles in cancer progression. However, the role of acidic extracellular pH in cancer progression is not studied as extensively as that of hypoxia. Here, we show that extracellular acidic pH (pH 6.8) triggered activation of sterol regulatory element-binding protein 2 (SREBP2) by stimulating nuclear translocation and promoter binding to its targets along with intracellular acidification. Interestingly, inhibition of SREBP2, but not SREBP1, suppressed the upregulation of low pH-induced cholesterol biosynthesis-related genes. Moreover, acyl-CoA synthetase short-chain family member 2 (ACSS2), a direct SREBP2 target, provided a growth advantage to cancer cells under acidic pH. Furthermore, acidic pH-responsive SREBP2 target genes were associated with reduced overall survival of cancer patients. Thus, our findings show that SREBP2 is a key transcriptional regulator of metabolic genes and progression of cancer cells, partly in response to extracellular acidification.
2017-01-25 | GSE93980 | GEO
Project description:The conditions of the tumor microenvironment, such as hypoxia and nutrient starvation, play critical roles in cancer progression. However, the role of acidic extracellular pH in cancer progression is not studied as extensively as that of hypoxia. Here, we show that extracellular acidic pH (pH 6.8) triggered activation of sterol regulatory element-binding protein 2 (SREBP2) by stimulating nuclear translocation and promoter binding to its targets along with intracellular acidification. Interestingly, inhibition of SREBP2, but not SREBP1, suppressed the upregulation of low pH-induced cholesterol biosynthesis-related genes. Moreover, acyl-CoA synthetase short-chain family member 2 (ACSS2), a direct SREBP2 target, provided a growth advantage to cancer cells under acidic pH. Furthermore, acidic pH-responsive SREBP2 target genes were associated with reduced overall survival of cancer patients. Thus, our findings show that SREBP2 is a key transcriptional regulator of metabolic genes and progression of cancer cells, partly in response to extracellular acidification.
2017-01-25 | GSE93988 | GEO
Project description:The conditions of the tumor microenvironment, such as hypoxia and nutrient starvation, play critical roles in cancer progression. However, the role of acidic extracellular pH in cancer progression is not studied as extensively as that of hypoxia. Here, we show that extracellular acidic pH (pH 6.8) triggered activation of sterol regulatory element-binding protein 2 (SREBP2) by stimulating nuclear translocation and promoter binding to its targets along with intracellular acidification. Interestingly, inhibition of SREBP2, but not SREBP1, suppressed the upregulation of low pH-induced cholesterol biosynthesis-related genes. Moreover, acyl-CoA synthetase short-chain family member 2 (ACSS2), a direct SREBP2 target, provided a growth advantage to cancer cells under acidic pH. Furthermore, acidic pH-responsive SREBP2 target genes were associated with reduced overall survival of cancer patients. Thus, our findings show that SREBP2 is a key transcriptional regulator of metabolic genes and progression of cancer cells, partly in response to extracellular acidification.
2017-01-25 | GSE93982 | GEO
Project description:In mammals, O2 and CO2 levels are tightly regulated and are altered under various pathological conditions. While the molecular mechanisms that participate in O2 sensing are well characterized, little is known regarding the signaling pathways that participate in CO2 signaling and adaptation. Here, we show that CO2 levels control a distinct cellular transcriptional response that differs from mere pH changes. Unexpectedly, we discovered that CO2 regulates the expression of cholesterogenic genes in a SREBP2-dependent manner and modulates cellular cholesterol accumulation. Molecular dissection of the underlying mechanism suggests that CO2 triggers SREBP2 activation through changes in endoplasmic reticulum membrane cholesterol levels. Collectively, we propose that SREBP2 participates in CO2 signaling and that cellular cholesterol levels can be modulated by CO2 through SREBP2
2023-10-06 | GSE196294 | GEO
Project description:We found that the number of tumor-infiltrating myofibroblasts was positively correlated to tumor acidification status in hepatocellular carcinoma (HCC). Hepatic stellate cells (HSCs), the predominant precursors of liver myofibroblasts, were activated and transdifferentiated into myofibroblasts under acidic culture condition. To identify the molecular phenotype of LX-2 cells in acidic culture conditions, we further conducted a gene expression profile analysis. LX-2 cells cultured in pH 7.2 or pH 6.2 medium separately for six days was used in gene expression microarray analysis.
2013-07-29 | E-GEOD-49301 | biostudies-arrayexpress
Project description:Microarray analysis of Aspergillus niger under conditions with differing combinations of carbon source, nitrogen source, nitrogen concentration, and culture pH Fermentor cultures were grown in minimal medium (MM) at a constant temperature of 30 ± 0.5 ºC and with differing combinations of carbon source (either 277.5 mM glucose or 333.0 mM xylose), nitrogen source (NH4Cl or NaNO3) and nitrogen concentration (4x: 282.4 mM; 8x: 564.8 mM), and pH (pH4 or pH5) of the medium (M. Braaksma, A.K. Smilde, M.J. van der Werf, P.J. Punt, submitted for publication). At different time points samples were collected, quenched immediately in methanol at -45 ºC and centrifuged at -20 ºC to remove supernatant. Part of the biomass was frozen into liquid nitrogen and stored at -80 ºC for microarray analysis. For each of the 16 culture conditions one sample was selected for microarray analysis; samples were collected either around the time point carbon source depleted or a considerable time (~24 h) after carbon souce depletion. In addition some technical duplicates were included.
2010-04-08 | GSE17329 | GEO
Project description:The physiological basis of the hypothesis that temperature is the primary governing factor of bacterial cell inactivation under otherwise non-growth permissive conditions was investigated. Application of simultaneous low pH (pH 3.5) and low water activity (aw = 0.9; 2.5 M NaCl) conditions, applied to L. monocytogenes strains Scott A and FW03/0035, and increasing incubation temperature from 25°C up to 45°C resulted in increased permeability to ethidium homodimer-1 and corresponded to accelerated declines in esterase activity and ATP basal levels but did not result in autolysis. Triphasic survival curves were readily observable when sufficiently large cell populations were inactivated at 25°C and 35°C; indicative of a mixture of sensitive and resistant sub-populations. Enrichment-based recovery experiments however indicate that the stress conditions eventually lead to complete loss of reproductive capacity, potentially corresponding to an irreversible collapse of pH homeostasis. Transcriptomic analyses were used to further obtain insights into the physiology of the inactivation process occurring at 25°C. RT-PCR, rifampin-enforced decay and microarray experiments revealed transcripts of tufA and other genes become substantially more stable during inactivation during exposure to combined low pH/aw and during non-growth permissive temperature exposure. Gene transcripts were delineated through K-means clustering that appear to be important for initial survival of combined low pH/aw and include an overrepresentation of SigB-activated genes, the response of which fades with increasing time of inactivation exposure. The microarray component of the experiments had the aim of determining: i) Gene expression responses of L. monocytogenes strain Scott A when exposed to a non-growth permissive environment consisting of a broth system acting as a food simulated environment adjusted to low pH (pH 3.5) and low water activity (2.5 M NaCl). ii) To examine the trend in gene expression over time under inactivating (killing) conditions by applying gene set (functional and regulatory) expression trend analysis and K-means cluster analysis. iii) To correlate this data to other physiological and mRNA quantification (real-time-PCR) data.
2009-10-30 | GSE18796 | GEO
Project description:MCF7 cells were grown in culture under low pH and physiological pH conditions in order to generate candidate biomarkers for tumor acidosis. SILAC was used to enable comparison of protein expression levels using relative quantification. Two biological replicates were prepared using "label flipping," and each fraction was analyzed in duplicate by LC-MS/MS. Sample nomenclature includes N for "normal" or physiological pH versus L for low pH as the first letter with H for "heavy" and L for "light" as the second letter. Therefore, one experiment is described as NH-LL, while the other is NL-LH. Fifteen IEF fractions were generated and analyzed with LC-MS/MS (RSLC and Orbitrap, Thermo) for each SILAC pair .
2020-07-07 | PXD002860 | Pride
Project description:Cancer cells are plastic, switching between signaling pathways to regulate growth under different conditions. In the tumor microenvironment this likely helps them evade therapies that target specific pathways. We must identify all possible signaling states and utilize them in drug screening programs to. One such state is characterized by expression of the transcription factor Hes3 and sensitivity to Hes3 knockdown and can be modeled in vitro by the use of defined culture conditions. Here we modeled this state in vitro, characterized it, and used it to identify drugs that target it. We cultured three primary human brain cancer cell lines, each from a different patient, under three different culture conditions (low, medium, and high Hes3 expression) and characterized gene regulation (RNA sequencing) and mechanical phenotype (real-time deformability assay). We also assessed gene expression regulation following Hes3 knockdown in conditions that maintain high Hes3 expression. We then employed a commonly used human brain tumor cell line to screen 1,600 FDA-approved compounds that specifically target the Hes3-high state in two different culture conditions (high and low Hes3). Cells from multiple patients behave similarly when placed under distinct culture conditions, in the assays described. We identified 37 FDA-approved compounds that specifically kill cancer cells in conditions characterized by high but not those characterized by low Hes3 expression. Our work reveals novel, potentially core signaling states in cancer, a strategy to identify treatments against them, and a set of putative drugs for potential repurposing.
2019-12-31 | GSE120647 | GEO
Project description:Rhizobium tropici CIAT899 is a nodule-forming α-proteobacterium displaying intrinsic resistance to several abiotic stress conditions such as low soil pH and high temperatures, which are common in tropical environments. It is a good competitor for Phaseolus vulgaris (common bean) nodule occupancy at low pH values, however little is known about the genetic or physiological basis of acid tolerance about gene expression under acidic conditions. To identify genes responding to pH stress we studied the transcriptomes of cells grown under different pH conditions. RNA was extracted from cells grown for several generations in minimal medium at 6.8 or 4.5 (adapted cells). In addition, we acid-shocked cells pre-grown at pH 6.8 for 45 minutes at pH 4.5. Transcriptomes were determined by RNA-Seq. From a total of 6289 protein-coding genes, 383 were found to be differentially expressed under acidic conditions versus control, among which 351 were induced and 32 repressed; only 11 genes were induced upon acid shock. The acid stress response of R. tropici CIAT899 is versatile: we found genes encoding response regulators and membrane transporters, but also enzymes involved in amino acid and carbohydrate metabolism and proton extrusion. Our findings enhance our understanding of the core genes that are important during the acid stress response in R. tropici.
2018-05-17 | GSE108074 | GEO