Summary of Study ST002963

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001843. The data can be accessed directly via it's Project DOI: 10.21228/M8GT6S This work is supported by NIH grant, U2C- DK119886.

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This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002963
Study TitleLC/MS detection for GSH and GSSG levels in KRAS-driven lung tumors with LKB1 or p53 deficiency, comparing cases with G6PD wild-type and G6PD knockout
Study SummaryIn this study, LC/MS was employed to assess whether G6PD loss affects the GSH and GSSG pool in Lkb1-deficient KRAS-driven lung tumors with LKB1 or p53 deficiency.
Institute
Rutgers Cancer Institute of New Jersey
Last NameGuo
First NameJessie
AddressRoom 3020, 195 Little Albany Stree (Rutgers Cancer Institute of New Jersey)
Emailyanxiang@cinj.rutgers.edu
Phone17327632262
Submit Date2023-10-26
Raw Data AvailableYes
Raw Data File Type(s)mzXML
Analysis Type DetailLC-MS
Release Date2024-01-16
Release Version1
Jessie Guo Jessie Guo
https://dx.doi.org/10.21228/M8GT6S
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR001843
Project DOI:doi: 10.21228/M8GT6S
Project Title:G6PD Maintains Redox Homeostasis and Biosynthesis in LKB1-Deficient KRAS-Driven Lung Cancer
Project Summary:Cancer cells depend on nicotinamide adenine dinucleotide phosphate (NADPH) to combat oxidative stress and support reductive biosynthesis. One major NAPDH production route is the oxidative pentose phosphate pathway (committed step: glucose-6-phosphate dehydrogenase, G6PD). Alternatives exist and can compensate in some tumors. Here, using genetically-engineered lung cancer model, we show that ablation of G6PD significantly suppresses KrasG12D/+;Lkb1-/- (KL) but not KrasG12D/+;p53-/- (KP) lung tumorigenesis. In vivo isotope tracing and metabolomics revealed that G6PD ablation significantly impaired NADPH generation, redox balance and de novo lipogenesis in KL but not KP lung tumors. Mechanistically, in KL tumors, G6PD ablation caused p53 activation that suppressed tumor growth. As tumor progressed, G6PD-deficient KL tumors increased an alternative NADPH source, serine-driven one carbon metabolism, rendering associated tumor-derived cell lines sensitive to serine/glycine depletion. Thus, oncogenic driver mutations determine lung cancer dependence on G6PD, whose targeting is a potential therapeutic strategy for tumors harboring KRAS and LKB1 co-mutations.
Institute:Rutgers Cancer Institute of New Jersey
Last Name:Guo
First Name:Jessie Yanxiang
Address:Room 3028, 195 Little Albany Street
Email:yanxiang@cinj.rutgers.edu
Phone:17327632262
Funding Source:R01CA237347-01A1, ACS 134036-RSG-19-165-01-TBG, GO2 Foundation for Lung Cancer, and Ludwig Princeton Branch of the Ludwig Institute for Cancer Research to J.Y.G. R01CA163591 and Ludwig Princeton Branch of the Ludwig Institute for Cancer Research to E.W. NIH P30 CA072720 to Rutgers Cancer Institute of New Jersey

Subject:

Subject ID:SU003076
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090
Gender:Male and female

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Genotype
SA3224191515-T-9G6pd-Knockout LSL-KrasG12D/+ LKB1-/-
SA3224201515-T-8G6pd-Knockout LSL-KrasG12D/+ LKB1-/-
SA3224211516-T-8G6pd-Knockout LSL-KrasG12D/+ LKB1-/-
SA3224221516-T-9G6pd-Knockout LSL-KrasG12D/+ LKB1-/-
SA3224231517-T-8G6pd-Knockout LSL-KrasG12D/+ LKB1-/-
SA3224241517-T-9G6pd-Knockout LSL-KrasG12D/+ LKB1-/-
SA3224251517-T-7G6pd-Knockout LSL-KrasG12D/+ LKB1-/-
SA3224264746-T-9G6pd-Knockout LSL-KrasG12D/+ p53-/-
SA3224275784-T-7G6pd-Knockout LSL-KrasG12D/+ p53-/-
SA3224285784-T-9G6pd-Knockout LSL-KrasG12D/+ p53-/-
SA3224294746-T-8G6pd-Knockout LSL-KrasG12D/+ p53-/-
SA3224305784-T-8G6pd-Knockout LSL-KrasG12D/+ p53-/-
SA3224314744-T-7G6pd-Knockout LSL-KrasG12D/+ p53-/-
SA3224324746-T-7G6pd-Knockout LSL-KrasG12D/+ p53-/-
SA3224334744-T-8G6pd-Knockout LSL-KrasG12D/+ p53-/-
SA3224344744-T-9G6pd-Knockout LSL-KrasG12D/+ p53-/-
SA3224353095-T-9G6pd-wild type LSL-KrasG12D/+ LKB1-/-
SA3224363096-T-9G6pd-wild type LSL-KrasG12D/+ LKB1-/-
SA3224373095-T-7G6pd-wild type LSL-KrasG12D/+ LKB1-/-
SA3224383096-T-8G6pd-wild type LSL-KrasG12D/+ LKB1-/-
SA3224393096-T-7G6pd-wild type LSL-KrasG12D/+ LKB1-/-
SA3224403094-T-7G6pd-wild type LSL-KrasG12D/+ LKB1-/-
SA3224413094-T-8G6pd-wild type LSL-KrasG12D/+ LKB1-/-
SA3224423094-T-9G6pd-wild type LSL-KrasG12D/+ LKB1-/-
SA322443709-T-7G6pd-wild type LSL-KrasG12D/+ p53-/-
SA322444892-T-8G6pd-wild type LSL-KrasG12D/+ p53-/-
SA322445709-T-8G6pd-wild type LSL-KrasG12D/+ p53-/-
SA322446892-T-9G6pd-wild type LSL-KrasG12D/+ p53-/-
SA322447710-T-8G6pd-wild type LSL-KrasG12D/+ p53-/-
SA322448892-T-7G6pd-wild type LSL-KrasG12D/+ p53-/-
SA322449710-T-9G6pd-wild type LSL-KrasG12D/+ p53-/-
SA322450710-T-7G6pd-wild type LSL-KrasG12D/+ p53-/-
SA322451709-T-9G6pd-wild type LSL-KrasG12D/+ p53-/-
Showing results 1 to 33 of 33

Collection:

Collection ID:CO003069
Collection Summary:At 6-8 weeks of age, mice were intranasally infected with Lenti-Cre (University of Iowa Viral Vector Core) at 5×106 plaque-forming units (pfu) per mouse to induce lung tumors. At 12 weeks post tumor induction, mice were euthanized for rapid lung tumors collection.
Sample Type:Lung tumors

Treatment:

Treatment ID:TR003085
Treatment Summary:Samples were taken from the mouse model. This model was generated as described in the collection section. No additional treatment was done.

Sample Preparation:

Sampleprep ID:SP003082
Sampleprep Summary:Approximately 20 mg of tumor samples were precisely weighed and placed into a pre-cooled tube. The tissue samples were then pulverized using the Cryomill. Pre-cooled extraction buffer consisting of methanol: acetonitrile: H2O (40:40:20, V/V) with 0.5% formic acid (Sigma-Aldrich, # F0507-100ML) was added to the resulting powder (40 μL of solvent per mg of tumors). The samples were then vortexed for 15 seconds and incubated on ice for 10 minutes. Subsequently, 15% NH4HCO3 solution (5% V/V of the extraction buffer) was used to neutralize the samples. Then all samples were vortexed again for 10 seconds and centrifuged at 4°C, 13,000 × g for 20 minutes. The resulting supernatant was transferred to LC-MS vials for subsequent analysis.

Combined analysis:

Analysis ID AN004864
Analysis type MS
Chromatography type Reversed phase
Chromatography system Thermo Scientific Vanquish HPLC
Column Waters XBridge BEH Amide (150 × 2.1 mm, 2.5 μm)
MS Type ESI
MS instrument type Orbitrap
MS instrument name Thermo Q Exactive Plus Orbitrap
Ion Mode NEGATIVE
Units Ion count

Chromatography:

Chromatography ID:CH003672
Instrument Name:Thermo Scientific Vanquish HPLC
Column Name:Waters XBridge BEH Amide (150 × 2.1 mm, 2.5 μm)
Column Temperature:25
Flow Gradient:The composition of mobile phase B varied over time as follows: 0 min, 100%; 3 min, 100%; 3.2 min, 90%; 6.2 min, 90%; 6.5 min, 80%; 10.5 min, 80%; 10.7 min, 70%; 13.5 min, 70%; 13.7 min, 45%; 16 min, 45%; 16.5 min, 100%.
Flow Rate:0.3 mL/min
Solvent A:95% water; 5% acetonitrile; 20 mmol/L NH3AC; 20 mmol/L NH3OH, pH~9
Solvent B:80% acetonitrile; 20% water; 20 mmol/L NH3AC; 20 mmol/L NH3OH, pH~9
Chromatography Type:Reversed phase

MS:

MS ID:MS004608
Analysis ID:AN004864
Instrument Name:Thermo Q Exactive Plus Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:-
Ion Mode:NEGATIVE
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