Summary of Study ST000644

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 PR000459. The data can be accessed directly via it's Project DOI: 10.21228/M8QP56 This work is supported by NIH grant, U2C- DK119886.

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Study IDST000644
Study TitleTrace 13C-glucose, 13C-glutamine, and 13C-serine in genetically engineered pancreatic cell lines through ceramides (part III)
Study SummaryTrace 13C-glucose, 13C-glutamine, and 13C-serine in genetically engineered pancreatic cell lines through ceramides
Institute
Mayo Clinic
Last NameLunt
First NameSophia
AddressMichigan State University 410B Biochemistry Building 603 Wilson Road East Lansing, MI 48824
Emailsophia@msu.edu
Phone517-432-4886
Submit Date2017-06-23
Analysis Type DetailLC-MS
Release Date2019-07-17
Release Version1
Sophia Lunt Sophia Lunt
https://dx.doi.org/10.21228/M8QP56
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR000459
Project DOI:doi: 10.21228/M8QP56
Project Title:Role of the Serine Biosynthesis Pathway in Supporting the Warburg Effect of Pancreatic Cancer Cells
Project Summary:Pancreatic cancer cells metabolize glucose differently than normal adult cells, relying on aerobic glycolysis even in oxygen-rich environments. This phenomenon, known as the Warburg effect, is the basis of PET scans for tumor imaging and diagnosis, but a definitive explanation for how this benefits cancer cells has remained elusive, and altered cell metabolism has not been fully exploited for therapeutic benefit. The Warburg effect is accompanied by expression of the M2 isoform of pyruvate kinase (PK); while many differentiated normal cells express PKM1, proliferating cells, including all cancer cells, express PKM1. We have generated both normal cell lines and pancreatic cancer cell lines that can be genetically controlled to express either PKM1 or PKM2. While normal proliferating cells stop proliferating when forced to express PKM1 rather than PKM2, pancreatic cancer cells proliferate just as rapidly with forced PKM1 expression. Preliminary data shows that pancreatic cancer cells upregulate the serine biosynthesis pathway during forced PKM1 expression. To probe the role of the serine biosynthesis pathway in supporting cancer proliferation in the context of isoform-specific PK expression, we have targeted genes in the serine biosynthesis pathway using the CRISPR/Cas9 system and generated pancreatic cancer knockout cell lines. The proposed research will use isotope-labeled precursors and genetic engineering to identify the metabolic dependencies of pancreatic cancer cells. Genetically engineered pancreatic cancer cell lines cultured with 13C-glucose, 13C-glutamine, or 13C-serine will be extracted and sent to the Mayo Clinic Metabolomics Resource Core for isotopic enrichment analysis of various amino acids, TCA cycle metabolites, fatty acids, and sphingolipids. This work will provide crucial first insight for altered metabolism of pancreatic cancer cells that can lead to novel metabolic targets for effectively treating pancreatic cancer.
Institute:Mayo Clinic
Last Name:Lunt
First Name:Sophia
Address:Michigan State University 410B Biochemistry Building 603 Wilson Road East Lansing, MI 48824
Email:sophia@msu.edu
Phone:517-432-4886
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