Impact of chronic extracellular acidosis on gene expression in mammary and pancreatic cancer cell lines
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE152345 | GEO | 2020/06/13
REPOSITORIES: GEO
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Project description:[1] Lactic acidosis time course: MCF7 cells were exposed to lactic acidosis for different length of time. We used microarrays to examine the genomic programs of cells incubated under lactic acidosis for different length of time [2] Metabolic profiling: MCF7 cells were exposed to control condition, 25mM lactic acidosis, glucose deprivation (zero glucose) and hypoxia (1% oxygen level). [3] Mouse study: Lactic acidosis triggers starvation response with paradoxical induction of TXNIP through MondoA. Wild-type mouse embryo fibroblasts (MEFs) and TXNIP-null MEFs were exposed to Ctrl versus lactic acidosis conditions for 24hrs and the RNAs from cells were extracted with MiRVana kit (Ambion) and applied to Affymetrix 430A mouse chips We used microarrays to examine the genomic programs of cells incubated under different microenvironmental stresses. [1] Lactic acidosis time course: MCF7 cells were exposed to lactic acidosis for 1, 4, 12 and 24 hours. [2] Metabolic profiling: MCF7 cells were exposed to lactic acidosis, glucose deprivation and hypoxia for 4hours. [3] wild-type mouse embryo fibroblasts (MEFs) and TXNIP-null MEFs were exposed to Ctrl versus lactic acidosis conditions for 24hrs.
2010-09-27 | E-GEOD-19123 | biostudies-arrayexpress
Project description:To understand the effect of lactic acidosis in cholangiocarcinoma cell line. Cells were cultured in different conditions: lactic acidosis, lactosis, acidosis and control. We found that lactic acidosis promoted aggressiveness of cancer cells and reprograming of metabolic.
2022-10-12 | GSE215085 | GEO
Project description:Lactic acidosis and hypoxia are two prominent tumor microenvironmental stresses that are both known to exert important influences on gene expression and phenotypes of cancer cells. But very little is known about the cross-talk and interaction between these two stresses. We performed gene expression analysis of MCF7 cells exposed to lactic acidosis, hypoxia and combined lactic acidosis and hypoxia. We found the hypoxia response elicited under hypoxia was mostly abolished upon simultaneous exposure to lactic acidosis. The repression effects are due to loss of HIF-1α protein synthesis under lactic acidosis. In addition, we showed lactic acidosis strongly synergizes with hypoxia to activate the unfold protein response (UPR) and inflammation response which are highly similar to amino acid deprivation responses (AAR). The statistical factor analysis of hypoxia and lactic acidosis responses indicated that ATF4 locus, an important activator in the UPR/AAR pathway, is amplified in subsets of breast tumors and cancer cell lines. Varying ATF4 levels dramatically affect the ability to survive the post-stress recovery from hypoxia and lactic acidosis and may suggest its selection of ATF4 amplification in human cancers. These data suggest that lactic acidosis interacts with hypoxia by both inhibiting the canonical hypoxia response and while activating the UPR and inflammation response. Gain of ATF4 locus may offer survival advantages to allow successful adaptation to frequent fluctuations of oxygen and acidity in tumor microenvironment. Collectively, our studies have provided linkage between the short-term transcriptional responses to the long term selection of the DNA copy number alterations (CNAs) under tumor microenvironmental stresses. RNAs from MCF7 cells exposed to control condition (ambient air ~21% O2, no lactate and neutral pH), lactic acidosis (ambient air, 10 mM Lactate and pH 6.7), hypoxia (1% pO2, no lactate and neutral pH) and the combined lactic acidosis and hypoxia (1% pO2, 10 mM Lactate and pH 6.7) condition for 24 hours were extracted by miRVana kits (Ambion) and hybridized to Affymetrix Human genome 133A 2.0 arrays with standard protocol.
2012-02-27 | E-GEOD-29406 | biostudies-arrayexpress
Project description:[1] Lactic acidosis time course: MCF7 cells were exposed to lactic acidosis for different length of time. We used microarrays to examine the genomic programs of cells incubated under lactic acidosis for different length of time [2] Metabolic profiling: MCF7 cells were exposed to control condition, 25mM lactic acidosis, glucose deprivation (zero glucose) and hypoxia (1% oxygen level). [3] Mouse study: Lactic acidosis triggers starvation response with paradoxical induction of TXNIP through MondoA. Wild-type mouse embryo fibroblasts (MEFs) and TXNIP-null MEFs were exposed to Ctrl versus lactic acidosis conditions for 24hrs and the RNAs from cells were extracted with MiRVana kit (Ambion) and applied to Affymetrix 430A mouse chips We used microarrays to examine the genomic programs of cells incubated under different microenvironmental stresses.
2010-09-27 | GSE19123 | GEO
Project description:Acidosis is a hallmark of the tumor microenvironment caused by the metabolic switch from glucose oxidative phosphorylation to glycolysis. It has been largely associated with tumor growth and progression, nevertheless, how acidosis promotes metastatic dissemination remains largely unknown. In this study, we established a long-term acidosis model using patient-derived lung cancer cells. By comparing xenograft inoculates at the cluster sizes of lung cancer circulating tumor cells, the acidosis cells display significantly higher incidence of secondary tumor establishment than their neutral pH counterparts. Transcriptomics analyses reveal a profound remodeling of the extracellular matrix in the acidosis cells, featuring the upregulation of ITGA4 and HAS3 genes, In clinical specimen, overexpression of both ITGA4 and HAS3 proteins are associated with primary tumors with metastatic ability, and their distribution is markedly accentuated around vascular mimicry structures in secondary tumors. We show that acidosis cells display higher ability of vascular mimicry in vitro, and are enriched in ABC transporter-dependent side population cells. Our data support that acidosis drives tumor metastatic colonization via enhanced extracellular matrix remodeling and vascular mimicry. Assessment on the prognostic value of tumor acidosis for metastasis and possible treatment directions are discussed.
2023-05-21 | GSE200546 | GEO
Project description:Lactic acidosis and hypoxia are two prominent tumor microenvironmental stresses that are both known to exert important influences on gene expression and phenotypes of cancer cells. But very little is known about the cross-talk and interaction between these two stresses. We performed gene expression analysis of MCF7 cells exposed to lactic acidosis, hypoxia and combined lactic acidosis and hypoxia. We found the hypoxia response elicited under hypoxia was mostly abolished upon simultaneous exposure to lactic acidosis. The repression effects are due to loss of HIF-1α protein synthesis under lactic acidosis. In addition, we showed lactic acidosis strongly synergizes with hypoxia to activate the unfold protein response (UPR) and inflammation response which are highly similar to amino acid deprivation responses (AAR). The statistical factor analysis of hypoxia and lactic acidosis responses indicated that ATF4 locus, an important activator in the UPR/AAR pathway, is amplified in subsets of breast tumors and cancer cell lines. Varying ATF4 levels dramatically affect the ability to survive the post-stress recovery from hypoxia and lactic acidosis and may suggest its selection of ATF4 amplification in human cancers. These data suggest that lactic acidosis interacts with hypoxia by both inhibiting the canonical hypoxia response and while activating the UPR and inflammation response. Gain of ATF4 locus may offer survival advantages to allow successful adaptation to frequent fluctuations of oxygen and acidity in tumor microenvironment. Collectively, our studies have provided linkage between the short-term transcriptional responses to the long term selection of the DNA copy number alterations (CNAs) under tumor microenvironmental stresses.
2012-02-27 | GSE29406 | GEO
Project description:The accumulation of acidic metabolic waste products within the tumor microenvironment profoundly inhibits effector functions of tumor-infiltrating lymphocytes (TILs). However, it is unclear whether extracellular-acidosis impacts T cell metabolic fitness and differentiation status. Here, we surprisingly found that prolonged acid exposure reprogrammed T cell intracellular metabolism and mitochondrial fitness, and preserved T cell stemness. Elevated extracellular-acidosis impaired methionine uptake and metabolism via downregulating SLC7A5, therefore altering H3K27me3 deposition at the promoters of crucial T cell stemness genes. These changes promoted the maintenance of a “stem-like memory” state and improved long-term in vivo persistence and anti-tumor efficacy. Our findings not only reveal the unexpected roles of extracellular-acidosis in the maintenance of stem-like properties of T cells, but also advance our understanding of the direct involvement of methionine metabolism in T cell stemness.
2022-12-05 | GSE216622 | GEO
Project description:The accumulation of acidic metabolic waste products within the tumor microenvironment profoundly inhibits effector functions of tumor-infiltrating lymphocytes (TILs). However, it is unclear whether extracellular-acidosis impacts T cell metabolic fitness and differentiation status. Here, we surprisingly found that prolonged acid exposure reprogrammed T cell intracellular metabolism and mitochondrial fitness, and preserved T cell stemness. Elevated extracellular-acidosis impaired methionine uptake and metabolism via downregulating SLC7A5, therefore altering H3K27me3 deposition at the promoters of crucial T cell stemness genes. These changes promoted the maintenance of a “stem-like memory” state and improved long-term in vivo persistence and anti-tumor efficacy. Our findings not only reveal the unexpected roles of extracellular-acidosis in the maintenance of stem-like properties of T cells, but also advance our understanding of the direct involvement of methionine metabolism in T cell stemness.
2022-12-05 | GSE216621 | GEO
Project description:Impact of chronic extracellular acidosis on gene expression in mammary and pancreatic cancer cell lines
| PRJNA639069 | ENA
Project description:Human Mammalian Epithelial Cells (HMEC) were exposed to different environmental stresses, including hypoxia, lactic acidosis, the combination of hypoxia and lactic acidosis, lactosis , as well as acidosis. We used microarrays to examine the genomic programs of cells incubated under different microenvironments. Experiment Overall Design: HMEC cells were exposed to different environmental stresses and RNAs were extracted and put on Affymetrix microarrays. We gathered RNAs from cells grown in regular media (control), lactic acidosis, hypoxia, the combinatino of lactic acidosis and hypoxia, lactosis, as well as acidosis.
2009-01-13 | E-GEOD-9649 | biostudies-arrayexpress