Summary of project PR002024
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 PR002024. The data can be accessed directly via it's Project DOI: 10.21228/M80C0P This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002024 |
| Project DOI: | doi: 10.21228/M80C0P |
| Project Title: | A Covalent Creatine Kinase Inhibitor Ablates Glioblastoma Migration and Sensitizes Tumors to Oxidative Stress |
| Project Type: | LC-MS/MS |
| Project Summary: | Glioblastoma is a Grade 4 primary brain tumor defined by therapy resistance, diffuse infiltration, and near-uniform lethality. The underlying mechanisms are unknown, and no treatment has been curative. Using a recently developed kinase inhibitor (CKi), we explored the role of this inhibitor on GBM biology in vitro. While CKi minimally impacted GBM cell proliferation and viability, it significantly affected migration. In established GBM cell lines and patient-derived xenografts, CKi ablated both the migration and invasion of GBM cells. CKi also hindered radiation-induced migration. RNA-seq revealed a decrease in invasion-related genes, with an unexpected increase in glutathione metabolism and ferroptosis protection genes post-CKi treatment. The effects of CKi could be reversed by the addition of cell-permeable glutathione. Carbon-13 metabolite tracing indicated heightened glutathione biosynthesis post-CKi treatment. Combinatorial CKi blockade and glutathione inhibition or ferroptosis activation abrogated cell survival. Our data demonstrated that CKi perturbs promigratory and anti-ferroptotic roles in GBM, identifying the creatine kinase axis as a druggable target for GBM treatment. |
| Institute: | Northwestern University, Feinberg School of Medicine |
| Department: | Neurological Surgery |
| Laboratory: | Jason Miska |
| Last Name: | Miska |
| First Name: | Jason |
| Address: | 676 N St. Clair |
| Email: | jason.miska@northwestern.edu |
| Phone: | 8478678201 |
Summary of all studies in project PR002024
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003262 | A Covalent Creatine Kinase Inhibitor Ablates Glioblastoma Migration and Sensitizes Tumors to Oxidative Stress. | Homo sapiens | Northwestern University, Feinberg School of Medicine | MS | 2024-06-18 | 1 | 12 | Uploaded data (700.2M)* |
