Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA143495 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Human tumors often contain slowly proliferating cancer cells that resist treatment but we do not know precisely how these cells arise. We show that rapidly proliferating cancer cells can divide asymmetrically to produce slowly proliferating “G0-like” progeny that are enriched following chemotherapy in breast cancer patients. Asymmetric cancer cell division results from asymmetric suppression of AKT/PKB kinase signaling in one daughter cell during telophase of mitosis. Moreover, inhibition of AKT signaling with small molecule drugs can induce asymmetric cancer cell division and the production of slow proliferators. Cancer cells therefore appear to continuously flux between symmetric and asymmetric division depending on the precise state of their AKT signaling network. This model may have significant implications for understanding how tumors grow, evade treatment, and recur. 3 replicates each of MCF7 Reactive Oxygen Species (ROS) high, HCT116 ROS high, MCF7 ROS low, and HCT116 ROS low.
2011-07-14 | E-GEOD-30465 | biostudies-arrayexpress
Project description:Human tumors often contain slowly proliferating cancer cells that resist treatment but we do not know precisely how these cells arise. We show that rapidly proliferating cancer cells can divide asymmetrically to produce slowly proliferating “G0-like” progeny that are enriched following chemotherapy in breast cancer patients. Asymmetric cancer cell division results from asymmetric suppression of AKT/PKB kinase signaling in one daughter cell during telophase of mitosis. Moreover, inhibition of AKT signaling with small molecule drugs can induce asymmetric cancer cell division and the production of slow proliferators. Cancer cells therefore appear to continuously flux between symmetric and asymmetric division depending on the precise state of their AKT signaling network. This model may have significant implications for understanding how tumors grow, evade treatment, and recur.
2011-07-15 | GSE30465 | GEO
Project description:Self-renewal programs in leukemia stem cells (LSCs) predict poor prognosis in acute myeloid leukemia (AML) patients. We identified CD4+ T cell-derived interleukin (IL) 21 as an important negative regulator of self-renewal of murine and human LSCs, but not hematopoietic stem cells. IL21/IL21R signaling favored asymmetric cell division and differentiation in LSCs through accumulation of reactive oxygen species (ROS) and activation of p38-MAPK signaling, resulting in reduced LSCs number and significantly prolonged survival in murine AML models. In human AML, serum IL21 at diagnosis was identified as an independent positive prognostic biomarker for outcome and correlated with better survival and higher complete remission rate in patients that underwent high-dose chemotherapy. IL21 inhibited primary AML LSCs function in vitro by activating ROS and p38-MAPK signaling and this effect was enhanced by cytarabine treatment. Consequently, promoting IL21/IL21R signaling on LSCs may be a novel approach to decrease stemness and increase differentiation in AML.
2024-10-12 | GSE241171 | GEO
Project description:Self-renewal programs in leukemia stem cells (LSCs) predict poor prognosis in acute myeloid leukemia (AML) patients. We identified CD4+ T cell-derived interleukin (IL) 21 as an important negative regulator of self-renewal of murine and human LSCs, but not hematopoietic stem cells. IL21/IL21R signaling favored asymmetric cell division and differentiation in LSCs through accumulation of reactive oxygen species (ROS) and activation of p38-MAPK signaling, resulting in reduced LSCs number and significantly prolonged survival in murine AML models. In human AML, serum IL21 at diagnosis was identified as an independent positive prognostic biomarker for outcome and correlated with better survival and higher complete remission rate in patients that underwent high-dose chemotherapy. IL21 inhibited primary AML LSCs function in vitro by activating ROS and p38-MAPK signaling and this effect was enhanced by cytarabine treatment. Consequently, promoting IL21/IL21R signaling on LSCs may be a novel approach to decrease stemness and increase differentiation in AML.
2024-10-12 | GSE241170 | GEO
Project description:Self-renewal programs in leukemia stem cells (LSCs) predict poor prognosis in acute myeloid leukemia (AML) patients. We identified CD4+ T cell-derived interleukin (IL) 21 as an important negative regulator of self-renewal of murine and human LSCs, but not hematopoietic stem cells. IL21/IL21R signaling favored asymmetric cell division and differentiation in LSCs through accumulation of reactive oxygen species (ROS) and activation of p38-MAPK signaling, resulting in reduced LSCs number and significantly prolonged survival in murine AML models. In human AML, serum IL21 at diagnosis was identified as an independent positive prognostic biomarker for outcome and correlated with better survival and higher complete remission rate in patients that underwent high-dose chemotherapy. IL21 inhibited primary AML LSCs function in vitro by activating ROS and p38-MAPK signaling and this effect was enhanced by cytarabine treatment. Consequently, promoting IL21/IL21R signaling on LSCs may be a novel approach to decrease stemness and increase differentiation in AML.
2024-10-12 | GSE241172 | GEO
Project description:In addition to driving tumorigenesis, oncogenes can create metabolic vulnerabilities in cancer cells. Here, we tested how the oncogenes AKT and MYC affect the ability to shift between respiration and glycolysis. Using immortalized mammary epithelial cellsMCF10A, we discovered constitutively active AKT but not MYC induced cell death in galactose culture, where cells must rely on oxidative phosphorylation for energy generation. However, the negative effects of AKT were short-lived, and AKT-expressing cells recommenced growth after ~15 days in galactose culture. To identify the mechanisms regulating AKT-mediated cell death, we first used metabolomics and found that AKT cells dying in galactose culture exhibited upregulated glutathione metabolism. Next, using shotgun proteomics, we discovered AKT cells dying in galactose upregulated proteins related to nonsense-mediated mRNA decay (NMD), a known response to oxidative stress. We therefore measured levels of reactive oxygen species (ROS) and discovered galactose culture induced ROS only in cells expressing AKT. Additionally, we found thatdiscovered the ROS scavenger catalase rescued AKT-expressing cells from galactose culture-induced cell death. We then demonstrated that breast cancer cell lines with constitutively active AKT signaling also exhibited cell death in galactose culture and rescue by catalase. Together, our results demonstrate that AKT but not MYC induces a metabolic vulnerability in cancer cells, namely the that restricted flexibility to use oxidative phosphorylation.
2020-03-19 | PXD015122 | Pride
Project description:Background: Arsenite is one of the most toxic chemical substances known and is assumed to exert detrimental effects on viability even at lowest concentrations. By contrast and unlike higher concentrations, we here find that exposure to low-dose arsenite promotes growth of cultured mammalian cells. In the nematode C. elegans, low-dose arsenite promotes resistance against thermal and chemical stressors, and extends lifespan of this metazoan, whereas higher concentrations reduce longevity. While arsenite causes a transient increase in reactive oxygen species (ROS) levels in C. elegans, co-exposure to ROS scavengers prevents the lifespan-extending capabilities of arsenite, indicating that transiently increased ROS levels act as transducers of arsenite effects on lifespan, a process known as mitohormesis. The RNA-seq data comprises 2 biological replicates for worms exposed to 100nM Arsenite 48h after L4 and 2 biological replicates of the same age as controls 4 samples: 2 mRNA profiles of C.elegans 48h after L4 exposed to Arsenite; 2 mRNA profiles of C.elegans 48h after L4 as controls (H20). The N2 wild type (var. Bristol) strain was used.
2013-04-23 | E-GEOD-46257 | biostudies-arrayexpress
Project description:Bifidobacterium longum strain BBMN68 is resistant to low concentrations of oxygen. In this study, a transcriptomic study was performed to detail the cellular response of B. longum strain BBMN68 to oxidative stress. Oxygen and its intermediate metabolites, reactive oxygen species (ROS), induced abundant changes in gene expression at the mRNA level. Increased expression was found for genes involved in ROS detoxification and the redox homeostasis system, protein and DNA synthesis and repair, the FeâS cluster assembly system, and biosynthesis of branched-chain amino acids and tetrahydrofolate. Among them, two classes of ribonucleotide reductase (RNR), which are important for deoxyribonucleotide biosynthesis, were rapidly and persistently induced: first, the class Ib RNR NrdHIEF and then the class III RNR NrdDG. The increased resistance to oxygen and hydrogen peroxide conferred by NADH oxidase was confirmed by its heterogeneous overexpression in B. longum strain NCC2705. In addition, cell-membrane and cell-wall compositions were modified, probably by an increase in cyclopropane fatty acids and a decrease in polysaccharides, respectively, resulting in improved cell hydrophobicity and autoaggregation; this subsequently reduced the permeation of dissolved oxygen into the cell. Taken together, the proposed cell model of B. longum responses to oxygen stress suggests that this bacterium employs a complex molecular defense mechanism against oxygen-induced stresses. Whole mRNA profiles of B. longum BBMN68 grown in the absence or presence of 3% oxygen were generated using AB SOLiD technology and differentially expressed genes were analyzed.
2016-01-26 | E-GEOD-65320 | biostudies-arrayexpress
Project description:IL-17-producing CD8+ (Tc17)T cells are implicated in the pathogenesis of multiple sclerosis (MS), thereby representing a promising target for therapy. We found that dimethyl fumarate (DMF), a first-line medication for MS upregulated reactive oxygen species (ROS) by glutathione depletion in murine Tc17 cells, which limited IL-17 and diverted Tc17 cells towards cytotoxic T lymphocyte (CTL) signature. DMF enhanced PI3K-AKT-FOXO1-T-bet- as well as STAT5-signaling leading to restricted permissive histone state at the Il17 locus. T-bet-deficiency, inhibiting PI3K-AKT, STAT5 or histone deacetylases prevented DMF-ROS-mediated IL-17 suppression. In MS patients with stable response, DMF suppressed IL-17 production by CD8+ T-cells and triggered diversion from Tc17 towards CTL signature along with enriched ROS-, PI3K-AKT-FOXO1-signaling, demonstrating comparable regulation across species. Accordingly, in the mouse model for MS, DMF limited Tc17-encephalitogenicity. Our findings disclose DMF-ROS-AKT-driven pathway, which selectively modulates Tc17 fate to ameliorate MS, thus opening avenue to develop markers and targets for specific therapy.
2018-07-11 | GSE116866 | GEO
Project description:IL-17-producing CD8+ (Tc17)T cells are implicated in the pathogenesis of multiple sclerosis (MS), thereby representing a promising target for therapy. We found that dimethyl fumarate (DMF), a first-line medication for MS upregulated reactive oxygen species (ROS) by glutathione depletion in murine Tc17 cells, which limited IL-17 and diverted Tc17 cells towards cytotoxic T lymphocyte (CTL) signature. DMF enhanced PI3K-AKT-FOXO1-T-bet- as well as STAT5-signaling leading to restricted permissive histone state at the Il17 locus. T-bet-deficiency, inhibiting PI3K-AKT, STAT5 or histone deacetylases prevented DMF-ROS-mediated IL-17 suppression. In MS patients with stable response, DMF suppressed IL-17 production by CD8+ T-cells and triggered diversion from Tc17 towards CTL signature along with enriched ROS-, PI3K-AKT-FOXO1-signaling, demonstrating comparable regulation across species. Accordingly, in the mouse model for MS, DMF limited Tc17-encephalitogenicity. Our findings disclose DMF-ROS-AKT-driven pathway, which selectively modulates Tc17 fate to ameliorate MS, thus opening avenue to develop markers and targets for specific therapy.
2018-07-11 | GSE116865 | GEO