Summary of project PR002140
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 PR002140. The data can be accessed directly via it's Project DOI: 10.21228/M80R74 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002140 |
| Project DOI: | doi: 10.21228/M80R74 |
| Project Title: | Blocking tryptophan catabolism reduces triple-negative breast cancer invasive capacity |
| Project Summary: | Anchorage-independent triple-negative breast cancer (TNBC) cells exhibit elevated levels of the tryptophan (TRP) catabolizing enzyme tryptophan 2,3-dioxygenase 2 (TDO2) compared to the same cells grown in two-dimensional culture. Tracing of 13C11-TRP demonstrated that anchorage-independent culture and/or inflammatory cytokines that activate nuclear factor kappa-light-chain-enhancer of activated B (NFκB) increase TRP catabolism and production of downstream catabolites such as kynurenine (KYN), which activate the aryl hydrocarbon receptor (AhR). TDO2 expression is heterogeneous within TNBC cell lines. To determine the function of TDO2, both pharmacologic inhibition and genetic manipulation were conducted. TDO2 knockdown revealed a compensatory increase in indoleamine 2,3-dioxygenase 1 (IDO1), a non-homologous TRP catabolizing enzyme, indicating that dual inhibition of these two enzymes is necessary to reliably block TRP catabolism. Thus, we tested a newly developed TDO2/IDO1 dual inhibitor, AT-0174, and found that it effectively inhibits TNBC TRP catabolism. Furthermore, AT-0174 treatment or AhR inhibitor significantly decreased TNBC anchorage-independent survival, invasive capacity, and expression of mesenchymal genes and protein, while exogenous KYN increased invasion through AhR-mediated ZEB1 expression. Thus, dual inhibition of TDO2/IDO1 may prove efficacious against TNBC progression. |
| Institute: | University of Colorado Anschutz Medical Campus |
| Laboratory: | Lab of Angelo D'Alessandro in collaboration with lab of Jennifer Richer |
| Last Name: | Haines |
| First Name: | Julie |
| Address: | 12801 E 17th Ave, Room 1303, Aurora, Colorado, 80045, USA |
| Email: | julie.haines@cuanschutz.edu |
| Phone: | 3037243339 |
Summary of all studies in project PR002140
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003484 | Metabolism of TNBC cell line MDA-MB-453 is altered by cytokines, TDO2 inhibition, or suspension growth conditions - cellular steady state metabolome and in vitro tracing with 13C11 tryptophan | Homo sapiens | University of Colorado Anschutz Medical Campus | MS | 2024-10-03 | 1 | 90 | Uploaded data (5.8G)* |
| ST003485 | Tryptophan metabolite profiling of cell supernatants (culture media) from TNBC cell lines with either overexpression or stable knockdown of TDO2. | Homo sapiens | University of Colorado Anschutz Medical Campus | MS | 2024-10-03 | 1 | 21 | Uploaded data (759.6M)* |
| ST003486 | Tryptophan metabolite profiling of cell supernatants (culture media) from TNBC cell line BT549 grown in suspension with TDO inhibition. | Homo sapiens | University of Colorado Anschutz Medical Campus | MS | 2024-10-03 | 1 | 12 | Uploaded data (423.9M)* |
| ST003487 | Tryptophan metabolite profiling of TNBC cell line BT549 grown in suspension with TDO inhibition. | Homo sapiens | University of Colorado Anschutz Medical Campus | MS | 2024-10-03 | 1 | 12 | Uploaded data (533.8M)* |
| ST003488 | Tryptophan metabolite profiling of cell supernatants (culture media) from TNBC cell line BT549 grown in suspension with TDO2 knockdown and IDO1 compensation. | Homo sapiens | University of Colorado Anschutz Medical Campus | MS | 2024-10-03 | 1 | 30 | Uploaded data (1.2G)* |
| ST003489 | Tryptophan pathway profiling of culture media from TNBC cell line MDA-MB-231 +/- inhibitors of the TDO/IDO pathway. | Homo sapiens | University of Colorado Anschutz Medical Campus | MS | 2024-10-03 | 1 | 9 | Uploaded data (1.1G)* |
| ST003490 | Metabolomics of culture media from TNBC cell line MDA-MB-453 +/- TDO2/IDO1 dual inhibition | Homo sapiens | University of Colorado Anschutz Medical Campus | MS | 2024-10-03 | 1 | 18 | Uploaded data (1.1G)* |
| ST003491 | Tryptophan/indole profiling of culture media from TNBC cell line SUM159PT with stable TDO2 overexpression. | Homo sapiens | University of Colorado Anschutz Medical Campus | MS | 2024-10-03 | 1 | 6 | Uploaded data (227.5M)* |
