Circular RNA expression profile in mitochondria fractions of liver tumour-initiating cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE223661 | GEO | 2023/01/25
REPOSITORIES: GEO
Similar Datasets
Project description:Bulk cancer cell populations are known to display distinct metabolic properties compared to their normal counterparts. However, relatively little is known about heterogeneity of metabolic properties within tumors. In this study we show that, analogous to some normal stem cells, breast tumor initiating cells (TICs, also called cancer stem cells) have distinct metabolic properties compared to non-tumorigenic cancer cells (NTCs). Transcriptome profiling using RNA-Seq revealed TICs under-express genes involved in mitochondrial oxidative phosphorylation and although TICs are relatively quiescent, they preferentially perform glycolysis over oxidative phosphorylation compared to NTCs. TICs contain fewer mitochondria and display lower expression and activity of pyruvate dehydrogenase (Pdh), a key regulator of oxidative phosphorylation. Metabolic reprogramming of TICs by pharmacologic activation of Pdh preferentially eliminates TICs in vitro and in vivo. Our findings reveal unique metabolic properties of TICs and indicate that metabolic reprogramming represents a promising strategy for targeting these cells. Examination transcriptome profiles for breast tumor initiating cells (TICs) and non-tumorigenic cells (NTCs)
2014-07-31 | E-GEOD-41286 | biostudies-arrayexpress
Project description:Bulk cancer cell populations are known to display distinct metabolic properties compared to their normal counterparts. However, relatively little is known about heterogeneity of metabolic properties within tumors. In this study we show that, analogous to some normal stem cells, breast tumor initiating cells (TICs, also called cancer stem cells) have distinct metabolic properties compared to non-tumorigenic cancer cells (NTCs). Transcriptome profiling using RNA-Seq revealed TICs under-express genes involved in mitochondrial oxidative phosphorylation and although TICs are relatively quiescent, they preferentially perform glycolysis over oxidative phosphorylation compared to NTCs. TICs contain fewer mitochondria and display lower expression and activity of pyruvate dehydrogenase (Pdh), a key regulator of oxidative phosphorylation. Metabolic reprogramming of TICs by pharmacologic activation of Pdh preferentially eliminates TICs in vitro and in vivo. Our findings reveal unique metabolic properties of TICs and indicate that metabolic reprogramming represents a promising strategy for targeting these cells.
2014-07-31 | GSE41286 | GEO
Project description:Following therapy, tumour-initiating cells (TICs) survive and give rise to second-line tumours. Gene set enrichment analysis of microarray data and microRNA analysis confirmed the validity of spheroid cultures as models of TICs for breast and prostate cancer and mesothelioma cell lines. Pathway analysis revealed increased Trp metabolism in all types of TICs with indoleamine 2,3-dioxygenase (IDO) as the rate-limiting enzyme. TICs also expressed higher levels of the Trp uptake system consisting of CD98 and LAT1 with functional consequences. Mitocans, represented by vitamin E (VE) analogues, suppressed IDO1 in TICs with functional mitochondrial complex II, a target for the agents. IDO1 expression was regulated via a mechanism involving both transcriptional and post-transcriptional mechanisms. IDO1 increase and its suppression by VE analogues were replicated in TICs from primary human glioblastomas. Our work points to Trp metabolism as a novel mechanism of TICs to bypass the immune surveillance and to VE analogues as agents that remove this ‘mimicry’.
2013-11-01 | GSE41980 | GEO
Project description:Following therapy, tumour-initiating cells (TICs) survive and give rise to second-line tumours. Gene set enrichment analysis of microarray data and microRNA analysis confirmed the validity of spheroid cultures as models of TICs for breast and prostate cancer and mesothelioma cell lines. Pathway analysis revealed increased Trp metabolism in all types of TICs with indoleamine 2,3-dioxygenase (IDO) as the rate-limiting enzyme. TICs also expressed higher levels of the Trp uptake system consisting of CD98 and LAT1 with functional consequences. Mitocans, represented by vitamin E (VE) analogues, suppressed IDO1 in TICs with functional mitochondrial complex II, a target for the agents. IDO1 expression was regulated via a mechanism involving both transcriptional and post-transcriptional mechanisms. IDO1 increase and its suppression by VE analogues were replicated in TICs from primary human glioblastomas. Our work points to Trp metabolism as a novel mechanism of TICs to bypass the immune surveillance and to VE analogues as agents that remove this ‘mimicry’. Total RNA obtained from from breast cancer (MCF7), mesothelioma (IstMes2) and prostate cancer (LNCaP) adherent cell lines was compared to their corresponding sphere cultures
2013-11-01 | E-GEOD-41980 | biostudies-arrayexpress
Project description:New approaches to cancer therapies could benefit from a better understanding of the molecular determinants critical to tumor initiating cells (TICs). Here we show that the metabolic enzyme glycine decarboxylase (GLDC) is critical for TICs in non-small cell lung cancer (NSCLC). From a broad range of primary NSCLC tumors, we isolated CD166+ lung TICs that consistently initiated tumorigenesis in NOD/SCID Il2rγ-/- mice. Lung TICs express high levels of the oncogenic stem cell factor LIN28B and the metabolic enzyme GLDC. Over-expression of GLDC and other glycine/serine metabolism enzymes, but not catalytically inactive GLDC, promotes cellular transformation and tumorigenesis. Metabolomic analysis found that GLDC induces dramatic changes in glycolysis and glycine/serine metabolism, leading to changes in pyrimidine metabolism to regulate cancer cell proliferation. Clinically, GLDC over-expression, observed in multiple cancer types, predicts poorer survival in lung cancer patients. Our findings establish a novel link between glycine metabolism and tumorigenesis, and provide novel targets for advancing anti-cancer therapy. Total RNA obtained from tumor sphere compared to CD166+ and CD166- selected cells of xenograft, primary tumor and normal donors
2011-10-25 | E-GEOD-33198 | biostudies-arrayexpress
Project description:New approaches to cancer therapies could benefit from a better understanding of the molecular determinants critical to tumor initiating cells (TICs). Here we show that the metabolic enzyme glycine decarboxylase (GLDC) is critical for TICs in non-small cell lung cancer (NSCLC). From a broad range of primary NSCLC tumors, we isolated CD166+ lung TICs that consistently initiated tumorigenesis in NOD/SCID Il2rγ-/- mice. Lung TICs express high levels of the oncogenic stem cell factor LIN28B and the metabolic enzyme GLDC. Over-expression of GLDC and other glycine/serine metabolism enzymes, but not catalytically inactive GLDC, promotes cellular transformation and tumorigenesis. Metabolomic analysis found that GLDC induces dramatic changes in glycolysis and glycine/serine metabolism, leading to changes in pyrimidine metabolism to regulate cancer cell proliferation. Clinically, GLDC over-expression, observed in multiple cancer types, predicts poorer survival in lung cancer patients. Our findings establish a novel link between glycine metabolism and tumorigenesis, and provide novel targets for advancing anti-cancer therapy.
2011-10-26 | GSE33198 | GEO
Project description:Background: cancer cells rely on glycolysis as main ATP source (Warbürg effect). Tumor-initiating cells (TICs) are the fraction of cells that give raise and repopulate tumors. TICs are exposed to prolonged periods of oxygen and glucose deprivation (OGD), as they live in a hypoxic niche and they withstand prolonged lack of blood vessels during initial tumorigenesis or metastasis formation (avascular phase). Warbürg effect is energetically inefficient; we hypothesize that TICs might have differential metabolic features. Tumor eradication requires killing TICS; finding such features would have therapeutic implications. Methodology/principal findings: 106 MDA-MB-231 breast-cancer cells (hereafter Wt) were exposed for 5 weeks to 0.2% oxygen and 0.1g/l glucose, recovering 9 clones. Both flow-cytometry (50-fold enrichment in the CD24-/CD44+/CD133+ population) and xenografts in NOD/SCID mice using 100 cells (75% vs. 16% engraftment) suggest that OGD-resistant clones are true TICs (hereafter “TIC clones”). TIC clones showed a 30-fold higher replication and viability (BRDU incorporation, colony assay) than Wt. When exposed to OGD, ATP-production dropped 5-fold in WT, but was maintained in TIC clones by increasing 5-fold the fatty acid and oxygen consumption. These properties were explained by lack of upregulation of HIF-1 alpha and PDK1, as well as an increase in ATP-synthase. Analysis with metabolic inhibitors (2-deoxyglucose, antimycin-A) confirmed glycolysis and mitochondrial respiration as main routes of metabolism for Wt and TIC clones respectively. Metabolomics revealed that glutamine catabolism generated the NADPH required to quench reactive oxygen species generated during mitochondrial respiration in TIC clones. Glutamine deprivation or mitochondrial blockers were able to abrogate the viability of TIC clones. Conclusions/significance: the TIC-fraction of a cancer cell population withstands prolonged OGD by switching from the Warbürg effect to mitochondrial respiration. Targeting this metabolic feature abrogates the survival of TICs.
2015-12-13 | GSE37340 | GEO
Project description:Here, we reveal that mitochondrial tRNA methylation is essential for efficient mitochondrial translation to dynamically shape cancer metabolism required for metastasis. Using oral squamous cell carcinoma (OSCC, SCC25 from ATCCR CRL-168TM and patient-derived cell lines with the names VDH01, VDH15) as a model system, we reveal the metabolic requirements of the metastasis-initiating tumour cell population. Only non-dividing tumour cells with high mitochondrial translation rates can invade and disseminate from primary tumours. Thus, inhibition of mitochondrial translation either through deletion of NSUN3 or through pharmacological inhibitors both block metastasis in orthotopic transplantation assays. Together, our study demonstrates that mitochondrial translation controls the metabolic reprogramming required for invasion and dissemination from the primary tumour.
| EGAS00001004765 | EGA
Project description:Analysis of PLCε-regulation of tyrosine metabolism at gene expression level. The hypothesis tested in the present study was that the PLCε pathway-directed transcriptional control play a key role for metabolic reprogramming in CD110+TICs after Kras extinction. Results provide important information of the response of colorectal CD110+TICs to inhibition of the PLCε pathway, such as specific stress-responsive genes, up- or down-regulated specific anabolic/catabolic cellular functions.
2015-12-01 | GSE75472 | GEO
Project description:Terminally exhausted CD8+ T-cells, which hold certain level of anti-tumour cytotoxicity but largely reduced proliferation capacity, contribute directly to tumour growth control. However, this subpopulation do not respond to immune checkpoint blockades or most existing immunotherapies and are difficult to be reactivated. Here, we show that a half-life extended interleukin (IL)-10/Fc fusion protein directly expands the terminally exhausted CD8+ TILs and sustains their effector functions through in vivo metabolic reprogramming, leading to eradication of established solid tumours and durable cures in a majority of treated mice when combined with adoptive T-cell transfer immunotherapy. Our results provide preclinical evidence that IL-10/Fc is a safe and highly effective therapy that acts on a specific subset of CD8+ TILs distinct from those responding to immune checkpoint blockades. Thus, IL-10/Fc could complement and synergize with existing cancer immunotherapies for enhanced efficacy and response rates. We find that IL-10/Fc reprograms T-cell metabolism by promoting oxidative phosphorylation through the mitochondrial pyruvate carrier, suggesting that metabolic reprogramming is sufficient to revitalize terminally exhausted CD8+ TILs.
2021-04-01 | GSE168990 | GEO