Summary of project PR002689
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 PR002689. The data can be accessed directly via it's Project DOI: 10.21228/M82R9H This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002689 |
| Project DOI: | doi: 10.21228/M82R9H |
| Project Title: | Histone methyltransferase PRDM9 promotes survival of drug-tolerant persister cells in glioblastoma |
| Project Summary: | Chemotherapy often kills a large fraction of cancer cells but leaves behind a small population of drug tolerant persister cells. These persister cells survive drug treatments through reversible, non-genetic mechanisms and cause tumour recurrence upon cessation of therapy. Here, we report a drug tolerance mechanism regulated by the germ-cell-specific H3K4 methyltransferase PRDM9. Through histone proteomic, transcriptomic, lipidomic, and ChIP-sequencing studies combined with CRISPR knockout and phenotypic drug screen, we identified that chemotherapy-induced PRDM9 upregulation promotes metabolic rewiring in glioblastoma stem cells, leading to chemotherapy tolerance. Mechanistically, PRDM9-dependent H3K4me3 at cholesterol biosynthesis genes enhances cholesterol biosynthesis, which persister cells rely on to maintain homeostasis under chemotherapy induced oxidative stress and lipid peroxidation. PRDM9 inhibition, combined with chemotherapy, resulted in strong anti-cancer efficacy in preclinical glioblastoma models, significantly enhancing the magnitude and duration of the antitumor response by eliminating persisters. These findings demonstrate a previously unknown role of PRDM9 in promoting metabolic reprogramming that enables the survival of drug-tolerant persister cells. |
| Institute: | The University of Sydney |
| Department: | School of Medical Sciences |
| Last Name: | Don |
| First Name: | Anthony |
| Address: | Office 3210, D17 Charles Perkins Centre, Camperdown, NSW, 2006, Australia |
| Email: | anthony.don@sydney.edu.au |
| Phone: | +612 8627 5578 |
| Publications: | Histone methyltransferase PRDM9 promotes survival of drug-tolerant persister cells in glioblastoma |
Summary of all studies in project PR002689
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST004262 | The lipidome of drug-resistant glioblastoma persister cells. | Homo sapiens | University of Sydney | MS | 2025-10-10 | 1 | 6 | Uploaded data (43.8M)* |
