Summary of project PR001989
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 PR001989. The data can be accessed directly via it's Project DOI: 10.21228/M8MT61 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001989 |
| Project DOI: | doi: 10.21228/M8MT61 |
| Project Title: | Proteo-metabolomics and patient tumor slice functional studies point to the centrality of amino acids for re-wired mitochondria in fibrolamellar carcinoma |
| Project Type: | LC-MS quantitative analysis |
| Project Summary: | Fibrolamellar carcinoma (FLC) is a rare, early-onset liver cancer. The five-year survival rate is low, and there is a critical need for new therapeutics. The primary driver in FLC is the fusion oncoprotein, DNAJ-PKAc, which remains challenging to target therapeutically. It is critical, therefore, to expand understanding of the FLC molecular landscape to identify druggable pathways/targets. To date, only one study has attempted to characterize the FLC proteome and metabolome, but with modest sample size (proteomics—n = 16 patient samples; metabolomics—n = 10 patient samples) and protein detection (n = 4620 proteins). We have performed the most comprehensive characterization of FLC in both proteomics (n = 23 patient samples; n = 8485 proteins) and metabolomics (n = 26 patient samples; n = 135 metabolites). Additionally, we have conducted respirometry analyses as well as RNAi- and small molecule inhibitor-mediated loss of function assays in FLC tumors and non-malignant liver tissue from patients. We propose a model of cellular energetics in FLC that centers on amino acids. Our model points to proline anabolism that is very likely mediated by ornithine aminotransferase hyperactivity and ornithine transcarbamylase hypoactivity with serine and glutamine catabolism providing the starting substrate. The metabolic rewiring in FLC proposed by our model, with a particular emphasis on mitochondria, can be exploited for therapeutic vulnerabilities. |
| Institute: | Cornell University |
| Department: | Biomedical Sciences |
| Laboratory: | Praveen Sethupathy |
| Last Name: | Long Jr. |
| First Name: | Donald |
| Address: | 618 Tower Road, Ithaca, New York, 14853, USA |
| Email: | dl964@cornell.edu |
| Phone: | 4355312013 |
| Funding Source: | Fibrolamellar Carcinoma Foundation |
| Contributors: | Guoan Zhang (Weill Cornell) |
Summary of all studies in project PR001989
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003193 | Metabolomics study on frozen tissue derived from the tumor and adjacent non-malignant liver tissue (NML) of patient afflicted with fibrolamellar carinoma (FLC) | Homo sapiens | Cornell University | MS | 2024-05-29 | 1 | 26 | Uploaded data (464.7M)* |
