Summary of project PR001775
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 PR001775. The data can be accessed directly via it's Project DOI: http://dx.doi.org/10.21228/M88M6V This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001775 |
| Project DOI: | http://dx.doi.org/10.21228/M88M6V |
| Project Title: | FGFR inhibition blocks NF-ĸB-dependent glucose metabolism and confers metabolic vulnerabilities in cholangiocarcinoma |
| Project Summary: | Genomic alterations that activate FGFR2 are common in intrahepatic cholangiocarcinoma (ICC) and confer sensitivity to FGFR inhibitor treatment. However, the depth and duration of responses are often limited. Here, we conducted integrative transcriptomics, metabolomics, and phosphoproteomics analysis of patient-derived models to define the pathways that fuel tumor growth downstream of oncogenic FGFR2 signaling in ICC and to uncover compensatory mechanisms associated with pathway inhibition. We find FGFR2-mediated activation of NF-kB maintains a highly glycolytic phenotype. Conversely, FGFR inhibition blocks glucose uptake and glycolysis while inciting a series of adaptive changes, including switching fuel source utilization to favor fatty acid oxidation and increasing mitochondrial fusion and autophagy. Accordingly, FGFR inhibitor efficacy is potentiated by combined mitochondrial targeting, an effect enhanced in xenograft models by intermittent fasting. Thus, we show that oncogenic FGFR2 signaling drives NF-kB-dependent glycolysis in ICC and that metabolic reprogramming in response to FGFR inhibition confers new targetable vulnerabilities. |
| Institute: | mgh |
| Last Name: | Zhen |
| First Name: | Yuanli |
| Address: | 185 cambridge street, room 4100 |
| Email: | yzhen1@mgh.harvard.edu |
| Phone: | 4698792279 |
Summary of all studies in project PR001775
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002835 | Investigation of FGFR signaling controlled metabolism in FGFR2-fusion+ intrahepatic cholangiocarcinoma | Homo sapiens | Massachusetts General Hospital | MS | 2024-03-20 | 1 | 30 | Uploaded data (3.4G)* |
| ST003106 | 13C-palmitate labeling experiment in ICC13-7 treated with DMSO or Infigratinib | Homo sapiens | Massachusetts General Hospital | MS | 2024-03-20 | 1 | 6 | Uploaded data (421.4M)* |
| ST003107 | Characterization of metabolic changes upon FGFR inhibition in ICC13-7 Xenograft | Mus musculus | Massachusetts General Hospital | MS | 2024-03-20 | 1 | 6 | Uploaded data (352.4M)* |
