Summary of project PR001954
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 PR001954. The data can be accessed directly via it's Project DOI: 10.21228/M84X6Q This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001954 |
| Project DOI: | doi: 10.21228/M84X6Q |
| Project Title: | Mitochondrial complex I promotes kidney cancer metastasis |
| Project Summary: | Most kidney cancers display metabolic dysfunction but how this relates to cancer progression in humans is unknown. We infused 13C-labeled nutrients during surgical tumour resection in over 80 patients with kidney cancer. Labeling from [U-13C]glucose varies across subtypes, indicating that the kidney environment alone cannot account for all metabolic reprogramming in these tumours. Compared to the adjacent kidney, clear cell renal cell carcinomas (ccRCC) display suppressed labelling of tricarboxylic acid (TCA) cycle intermediates in vivo and in organotypic cultures ex vivo, indicating that suppressed labeling is tissue intrinsic. Infusions of [1,2-13C]acetate and [U-13C]glutamine in patients, coupled with measurements of respiration in mitochondria isolated from kidneys and tumours, reveal electron transport chain (ETC) defects in ccRCC. However, ccRCC metastases unexpectedly have enhanced TCA cycle labeling compared to primary ccRCCs, indicating a divergent metabolic program during metastasis in patients. In mice, stimulating respiration or NADH recycling in kidney cancer cells is sufficient to promote metastasis, while inhibiting ETC complex I decreases metastasis. These findings indicate that metabolic properties and liabilities evolve during kidney cancer progression in humans, and that mitochondrial function is limiting for metastasis but not for growth at the original site. |
| Institute: | University of Texas Southwestern Medical Center at Dallas |
| Laboratory: | Ralph DeBerardinis, MD, PhD |
| Last Name: | Bezwada |
| First Name: | Divya |
| Address: | 5323 Harry Hines Boulevard, Dallas, TX 75390-8502 |
| Email: | dbezwada@scripps.edu |
| Phone: | 214.648-2587 |
Summary of all studies in project PR001954
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003143 | Mitochondrial complex I promotes kidney cancer metastasis | Homo sapiens | University of Texas Southwestern Medical Center at Dallas | MS | 2024-06-17 | 1 | 59 | Uploaded data (20.4G)* |
