Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA259203 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Metabolism is tightly coupled with the process of aging, and tumorigenesis. However, the mechanisms regulating metabolic properties in different contexts remain unclear. Cellular senescence is widely recognized as an important tumor suppressor function and accompanies metabolic remodeling characterized by increased mitochondrial oxidative phosphorylation (OXPHOS). Here we showed retinoblastoma (RB) is required for the increased OXPHOS in oncogene-induced senescent (OIS) cells. Combined metabolic and gene expression profiling revealed that RB mediated activation of the glycolytic pathway in OIS cells, causing upregulation of several glycolytic genes and concomitant increases in the levels of associated metabolites in the glycolytic pathway. Knockdown of these genes by small interfering RNAs (siRNAs) resulted in decreased mitochondrial respiration, suggesting that RB-mediated glycolytic gene activation promotes metabolic flux into the OXPHOS pathway. These results suggest that coordinate transcriptional activation of metabolic genes by RB enables OIS cells to maintain metabolically bivalent states that both glycolysis and OXPHOS are highly active. Collectively, our findings demonstrated a previously unrecognized function of RB in OIS cells. To understand the role of RB, we investigated the effect of RB1-knockdown in the transcription profile of oncogene-induced senescent (OIS) cells. IMR90 ER:Ras cells were treated with 100 nM 4-OHT for 6 days to induce senescence. RNA was isolated 6 days after OHT treatment and hybridized to Affymetrix microarrays. SiRNA transfection (control siRNA or siRB1) was performed 4 days before RNA isolation.
2015-05-26 | E-GEOD-60652 | biostudies-arrayexpress
Project description:Metabolism is tightly coupled with the process of aging, and tumorigenesis. However, the mechanisms regulating metabolic properties in different contexts remain unclear. Cellular senescence is widely recognized as an important tumor suppressor function and accompanies metabolic remodeling characterized by increased mitochondrial oxidative phosphorylation (OXPHOS). Here we showed retinoblastoma (RB) is required for the increased OXPHOS in oncogene-induced senescent (OIS) cells. Combined metabolic and gene expression profiling revealed that RB mediated activation of the glycolytic pathway in OIS cells, causing upregulation of several glycolytic genes and concomitant increases in the levels of associated metabolites in the glycolytic pathway. Knockdown of these genes by small interfering RNAs (siRNAs) resulted in decreased mitochondrial respiration, suggesting that RB-mediated glycolytic gene activation promotes metabolic flux into the OXPHOS pathway. These results suggest that coordinate transcriptional activation of metabolic genes by RB enables OIS cells to maintain metabolically bivalent states that both glycolysis and OXPHOS are highly active. Collectively, our findings demonstrated a previously unrecognized function of RB in OIS cells. To understand the role of RB, we investigated the effect of RB1-knockdown in the transcription profile of oncogene-induced senescent (OIS) cells.
2015-05-26 | GSE60652 | GEO
Project description:Expression of the BRAFV600E oncoprotein is known to cause benign lesions, for example melanocytic nevi (moles). In spite of the oncogenic function of mutant BRAF, these lesions are arrested by a cell-autonomous mechanism called Oncogene-Induced Senescence (OIS). Infrequently, nevi can progress to malignant melanoma, through mechanisms that are incompletely understood. To gain more insight into this vital tumor suppression mechanism, we performed a mass spectrometry-based screening of the proteome and phosphoproteome in cycling and senescent cells as well as cells that have abrogated senescence. Proteome analysis of senescent cells revealed the upregulation of established senescence biomarkers, including specific cytokines, but also several proteins not previously associated with senescence, including extracellular matrix-interacting. Using both general and targeted phosphopeptide enrichment by Ti4+-IMAC and phosphotyrosine antibody enrichment, we identified over 15,000 phosphorylation sites. Among the regulated phosphorylation sites we encountered components of the interleukin, BRAF/MAPK and CDK-retinoblastoma (Rb) pathways and several other factors. The extensive proteome and phosphoproteome dataset of BRAFV600E-expressing senescent cells provides molecular clues as to how OIS is initiated, maintained or evaded, serving as a comprehensive proteomic basis for functional validation.
2015-01-13 | PXD001068 | Pride
Project description:Expression of the BRAFV600E oncoprotein is known to cause benign lesions, for example melanocytic nevi (moles). In spite of the oncogenic function of mutant BRAF, these lesions are arrested by a cell-autonomous mechanism called Oncogene-Induced Senescence (OIS). Infrequently, nevi can progress to malignant melanoma, through mechanisms that are incompletely understood. To gain more insight into this vital tumor suppression mechanism, we performed a mass spectrometry-based screening of the proteome and phosphoproteome in cycling and senescent cells as well as cells that have abrogated senescence. Proteome analysis of senescent cells revealed the upregulation of established senescence biomarkers, including specific cytokines, but also several proteins not previously associated with senescence, including extracellular matrix-interacting. Using both general and targeted phosphopeptide enrichment by Ti4+-IMAC and phosphotyrosine antibody enrichment, we identified over 15,000 phosphorylation sites. Among the regulated phosphorylation sites we encountered components of the interleukin, BRAF/MAPK and CDK-retinoblastoma (Rb) pathways and several other factors. The extensive proteome and phosphoproteome dataset of BRAFV600E-expressing senescent cells provides molecular clues as to how OIS is initiated, maintained or evaded, serving as a comprehensive proteomic basis for functional validation.
2015-01-12 | PXD000523 | Pride
Project description:MCF7 breast cancer cells are a luminal-type breast cancer with moderate native levels of SIM2s. To determine effects of SIM2s on tumor progression, cells were stably transduced with SIM2si shRNA to knockdown expression, inducing an EMT effect. Microarray analysis was performed to determine genetic pathways involved in this phenotype. The coordination of cellular metabolism is a key factor in the progression of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC). Pathways regulating the balance between oxidative phosphorylation and glycolysis are unclear. We have found that transcription factor Singleminded-2s (SIM2s), commonly lost with breast cancer progression, contributes to metabolic regulation by controlling glycolytic flux and cellular senescence. Through promotion of p21 and cellular senescence, SIM2s decreases glycolytic enzyme activity and promotes oxidative phosphorylation in breast cancer. These, coupled with increased autophagy and ROS, inhibit tumor growth and metastasis. We use microarrays to detail the global gene programming changes that occur with loss of SIM2s gene expression. Scrambled and SIM2si cells were grown in triplicate for RNA extraction and hybridization on Amersham microarrays.
2013-02-08 | E-GEOD-44187 | biostudies-arrayexpress
Project description:Oxidative stress plays a critical role in liver tissue damage and in hepatocellular carcinoma (HCC) initiation and progression. However, the mechanisms that regulate autophagy and metabolic reprogramming during the generation of reactive oxygen species (ROS), and how ROS promotes tumorigenesis, still need to be fully understood. We show that protein kinase C (PKC) / loss in hepatocytes promotes autophagy and oxidative phosphorylation. This results in ROS generation, which through NRF2 drives HCC cell autonomously and non-autonomously. Although PKC / promotes tumorigenesis in oncogene-driven cancer models, emerging evidence demonstrate that it is a tumor suppressor in more complex carcinogenic processes. Consistently, PKC / levels negatively correlate with HCC histological tumor grade, establishing this kinase as a tumor suppressor in liver cancer.
2020-06-30 | GSE147800 | GEO
Project description:Oxidative stress plays a critical role in liver tissue damage and in hepatocellular carcinoma (HCC) initiation and progression. However, the mechanisms that regulate autophagy and metabolic reprogramming during the generation of reactive oxygen species (ROS), and how ROS promotes tumorigenesis, still need to be fully understood. We show that protein kinase C (PKC) / loss in hepatocytes promotes autophagy and oxidative phosphorylation. This results in ROS generation, which through NRF2 drives HCC cell autonomously and non-autonomously. Although PKC/ promotes tumorigenesis in oncogene-driven cancer models, emerging evidence demonstrate that it is a tumor suppressor in more complex carcinogenic processes. Consistently, PKC / levels negatively correlate with HCC histological tumor grade, establishing this kinase as a tumor suppressor in liver cancer.
2020-06-30 | GSE147778 | GEO
Project description:<p>We identified germline <a href="https://www.ncbi.nlm.nih.gov/gene/?term=23028">KDM1A</a> truncating mutations in patients with multiple myeloma (MM), and loss of heterozygosity (LOH) in tumors. KDM1A mutation burden is higher in sporadic MM patients than in controls, and mRNA levels are lower in MM compared with normal plasma cells. KDM1A pharmacological inhibition in vitro promotes myeloma cell proliferation, and in mice promotes plasma cell expansion, enhanced secondary immune response to T cell dependent antigens, and upregulation of MYC oncogene transcriptional targets. Our findings provide important new insights into the role of KDM1A to suppress B cell malignancies.</p>
| phs001819 | dbGaP
Project description:MCF7 breast cancer cells are a luminal-type breast cancer with moderate native levels of SIM2s. To determine effects of SIM2s on tumor progression, cells were stably transduced with SIM2si shRNA to knockdown expression, inducing an EMT effect. Microarray analysis was performed to determine genetic pathways involved in this phenotype. The coordination of cellular metabolism is a key factor in the progression of ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC). Pathways regulating the balance between oxidative phosphorylation and glycolysis are unclear. We have found that transcription factor Singleminded-2s (SIM2s), commonly lost with breast cancer progression, contributes to metabolic regulation by controlling glycolytic flux and cellular senescence. Through promotion of p21 and cellular senescence, SIM2s decreases glycolytic enzyme activity and promotes oxidative phosphorylation in breast cancer. These, coupled with increased autophagy and ROS, inhibit tumor growth and metastasis. We use microarrays to detail the global gene programming changes that occur with loss of SIM2s gene expression.
2013-02-08 | GSE44187 | GEO
Project description:Oxidative phosphorylation promotes primary melanoma invasion
| PRJNA602818 | ENA