Summary of project PR000459
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.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| 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 |
Summary of all studies in project PR000459
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST000642 | Trace 13C-glucose, 13C-glutamine, and 13C-serine in genetically engineered pancreatic cell lines through free fatty acids (part I) | Homo sapiens | Mayo Clinic | MS | 2019-07-17 | 1 | 18 | Not available |
| ST000643 | Trace 13C-glucose, 13C-glutamine, and 13C-serine in genetically engineered pancreatic cell lines through non-esterified fatty acids (part II) | Homo sapiens | Mayo Clinic | MS | 2019-07-17 | 1 | 54 | Not available |
| ST000644 | Trace 13C-glucose, 13C-glutamine, and 13C-serine in genetically engineered pancreatic cell lines through ceramides (part III) | Homo sapiens | Mayo Clinic | MS | 2019-07-17 | 1 | 54 | Not available |
