publication_authors:Locasale JW Results

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Organism

Mus musculus (26)

Technology

Microarray (26)

Platform

Affymetrix Mouse Genome 430 2.0 Array (mouse4302) (26)

Affymetrix Murine Genome U74A Version 2 Array (mgu74av2) (9)

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GSE32277

Kras is required for pancreatic tumor maintenance through regulation of hexosamine biosynthesis and the non-oxidative pentose phosphate pathway

Mus musculus
13 Downloadable Samples

Description

The maintenance of advanced malignancies relies on continued activity of driver oncogenes, although their rate-limiting role is highly context-dependent with respect to tumor types and associated genetic alterations. Oncogenic Kras mutation is the signature event in human pancreatic ductal adenocarcinoma (PDAC), serving a critical role in tumor initiation. Here, an inducible KrasG12D-driven p53 mutant PDAC mouse model establishes that advanced PDAC remains strictly dependent on continued KrasG12D expression and that KrasG12D serves a vital role in the control of tumor metabolism, through stimulation of glucose uptake and channeling of glucose intermediates through the hexosamine biosynthesis pathway (HBP) and the pentose phosphate pathway (PPP). Notably, these studies reveal that oncogenic Kras regulates ribose biogenesis. Unlike canonical models of PPP-mediated ribose biogenesis, we demonstrate that oncogenic Kras drives intermediates from enhanced glycolytic flux into the non-oxidative arm of the PPP, thereby decoupling ribose biogenesis from NADPNADPH-mediated redox control. Together, this work provides in vivo mechanistic insights into how oncogenic Kras promotes metabolic reprogramming in native tumors and illuminates potential metabolic targets that can be exploited for therapeutic benefit in Kras-driven PDAC.

Publication Title

Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism.

Alternate Accession IDs

E-GEOD-32277

Sample Metadata Fields

Specimen part, Treatment

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GSE12505

Plasmacytoid dendritic cells (pDCs) from E2-2 heterozygous mice

Mus musculus
4 Downloadable Samples

Description

Analysis of expression profiles of pDCs from wild type and heterozygous E2-2 mice. Results show the control by E2-2 of the expression of pDC-enriched genes.