Summary of project PR001303
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 PR001303. The data can be accessed directly via it's Project DOI: 10.21228/M89135 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001303 |
| Project DOI: | doi: 10.21228/M89135 |
| Project Title: | Unchecked oxidative stress is an insurmountable barrier for tumour cells that disseminate to skeletal muscle |
| Project Summary: | Skeletal muscle has been recognized as an inhospitable site for disseminated tumour cells (DTCs) for decades, yet its antimetastatic nature has eluded a thorough mechanistic description. Here, we show that DTCs traffic to and persist within skeletal muscle, raising the question as to how this tissue suppresses colonization. We employed mouse and organotypic culture models along with metabolomic profiling and ultimately find that oxidative stress is a principal suppressor of DTC proliferation in skeletal muscle. DTCs bypassed this oxidative constraint upon colonization of more fertile sites, but were unable to in muscle. Functional studies demonstrated that disrupting redox homeostasis via chemogenetic induction of reactive oxygen species slowed proliferation in lung. Conversely, enhancing antioxidant potential of tumour cells via ectopic expression of catalase allowed robust colonization of skeletal muscle. These findings reveal a profound metabolic bottleneck imposed on DTCs and sustained by skeletal muscle. Understanding this biology could reveal novel DTC vulnerabilities. |
| Institute: | University of Colorado Anschutz Medical Campus |
| Last Name: | Nemkov |
| First Name: | Travis |
| Address: | 12801 E 17th Avenue, RC-1 South, Rm 9403G, Aurora, CO, 80045, USA |
| Email: | travis.nemkov@cuanschutz.edu |
| Phone: | 303-724-3253 |
Summary of all studies in project PR001303
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002058 | Muscle/Lung/Tumor metabolomics | Mus musculus | University of Colorado Anschutz Medical Campus | MS | 2022-02-14 | 1 | 32 | Uploaded data (267.1M)* |
| ST002059 | 4T1 and SkM cells | Homo sapiens | University of Colorado Anschutz Medical Campus | MS | 2022-02-14 | 1 | 12 | Uploaded data (65.5M)* |
