Oncogenic kras maintains pancreatic tumors through regulation of anabolic glucose metabolismCitation Count is the number of times that this paper has been cited by oncogenic kras maintains pancreatic tumors through regulation of anabolic glucose metabolism published papers in the database. The Altmetric Attention Score is a weighted count of all of the online attention Altmetric have found for an individual research output. This includes mentions in public policy documents and references in Wikipedia, the mainstream news, social networks, blogs and more. More detail on dianabol methandienone comprimate 10mg weightings of each source and how they contribute to the attention score is available here. The Relative Citation Ratio RCR indicates the relative citation performance of an article when comparing its citation rate to that of ocnogenic articles in its area of research. A value of more than 1.
Tumor maintenance relies on continued activity of driver oncogenes, although their rate-limiting role is highly context dependent. Oncogenic Kras mutation is the signature event in pancreatic ductal adenocarcinoma PDAC , serving a critical role in tumor initiation. Transcriptome and metabolomic analyses indicate that Kras G12D serves a vital role in controlling tumor metabolism through stimulation of glucose uptake and channeling of glucose intermediates into the hexosamine biosynthesis and pentose phosphate pathways PPP.
These studies also reveal that oncogenic Kras promotes ribose biogenesis. National Center for Biotechnology Information , U. Didn't get the message? Add to My Bibliography. Generate a file for use with external citation management software. Abstract Tumor maintenance relies on continued activity of driver oncogenes, although their rate-limiting role is highly context dependent.
Comment in Pancreatic cancer: Mouse models link metabolism and deubiquitination with Kras. Images from this publication.
See all images 7 Free text. A Kaplan-Meier overall survival analysis for mice of indicated genotypes. Cohort size for each genotype is indicated. D MRI scan illustrating tumor area within the dotted line shrinkage following 7 days of doxy withdrawal.
The mice were pulled from doxy treatment at the indicated days and injected with BrdU. Pancreatic tumors were stained with antibodies to BrdU panels i, iv, vii, x , cleaved-caspase3 panels ii, v, viii, xi , and SMA panels iii, vi, ix, xii. B Pancreatic tumors from A were stained with antibodies to phospho-Erk panels i, iii, v, vii and phospho-S6 panels ii, iv, vi, viii.
Scale bar represents mm. Animals were kept on doxy for 2 weeks until tumors were fully established. Half of the animals were pulled off doxy for 24 hr at which point tumor lysate was prepared. Ras activity was measured with Raf-RBD pull-down assay. B Heat maps of the genes enriched in indicated metabolism pathways illustrate the changes in gene expression upon doxy withdrawal.
Expression levels shown are representative of log 2 values of each replicate from either xenograft tumors or cultured parental cell lines.
Red signal denotes higher expression relative to the mean expression level within the group and green signal denotes lower expression relative to the mean expression level within the group. C GSEA plot of steroid biosynthesis top , pyrimidine metabolism middle , and O-glycan biosynthesis bottom pathways based on the off-doxy versus on-doxy gene expression profiles.
NES denotes normalized enrichment score. A Summary of the changes in glycolysis upon Kras G12D inactivation. Metabolites that decrease upon doxy withdrawal are indicated with green arrows. Bar graphs indicate the relative expression levels of differentially expressed glycolytic enzymes that showed a significant decrease in the absence of doxy; the gene names for those enzymes that exhibited significant changes are also highlighted in the cartoon in blue.
Glycolytic enzymes whose change in expression was not significant are illustrated in gray. Cells were maintained in the presence or absence of doxy for 24 hr, at which point metabolite levels were measured from triplicates for each treatment condition. The averaged ratios of off-doxy over on-doxy levels for differentially regulated metabolites are represented in the heat map. Asterisks indicate metabolites involved in glucose metabolism that decrease upon doxy withdrawal.
Relative changes of glucose C or lactate D levels in the medium were measured and normalized to cell numbers. E Fold changes of glycolytic intermediates upon doxy withdrawal for 24 hr. Error bars represent SD of the mean.
Differentially expressed genes upon doxy withdrawal are highlighted in blue. B Fold change of metabolites in the HBP upon doxy withdrawal for 24 hr. E Western blot analysis for O-linked N-acetylglucosamine O-GlcNAc levels in cells maintained in the presence or absence of doxy for 24 hr.
For control samples, MEFs were cultured in the presence or absence of glucose for 24 hr. Tumor volumes were measured and data shown are representative of results from three independent cell lines.
C Fold changes for metabolites in the PPP upon doxy withdrawal for 24 hr. H Quantification of colony numbers. In parallel, cells were cultured in the presence or absence of doxy for 24 hr to serve as controls and relative mRNA levels of indicated metabolism genes were measured by QPCR.
B Schematic representation of the shift in glucose metabolism upon Kras G12D withdrawal. Microarray - SciCrunch Marmoset Gene list: Gene Annotation - SciCrunch.