Summary of project PR001314
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 PR001314. The data can be accessed directly via it's Project DOI: 10.21228/M8VT5T This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001314 |
| Project DOI: | doi: 10.21228/M8VT5T |
| Project Title: | A non-dividing population with high pyruvate dehydrogenase kinase activity drives metabolic heterogeneity and tumorigenesis in the intestine |
| Project Summary: | Although reprogramming of cellular metabolism is a hallmark of cancer, little is known about how metabolic reprogramming contributes to early stages of transformation. Here, we show that the histone deacetylase SIRT6 regulates tumor initiation during intestinal cancer by controlling glucose metabolism. Loss of SIRT6 results in increased number of intestinal stem cells (ISCs), which translates into enhanced tumor initiating potential in APCmin mice. More importantly, we found a metabolic compartmentalization within the intestinal epithelium and adenomas, where a rare population of cells exhibit features of Warburg-like metabolism characterized by high pyruvate dehydrogenase kinase (PDK) activity. Our results show that these cells are quiescent cells expressing +4 ISCs and enteroendocrine markers. Active glycolysis in these cells suppresses ROS accumulation and enhances their stem cell and tumorigenic potential. Our studies reveal that aerobic glycolysis represents a highly heterogeneous feature of cancer, and more importantly, they indicate that this metabolic adaptation occurs in non-dividing cells, suggesting a role for the Warburg effect beyond biomass production in tumors. |
| Institute: | Massachusetts General Hospital |
| Last Name: | Mostoslavsky |
| First Name: | Raul |
| Address: | 55 Fruit Street Boston, MA 02114 |
| Email: | rmostoslavsky@mgh.harvard.edu |
| Phone: | 617-643-3146 |
Summary of all studies in project PR001314
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002072 | A non-dividing population with high pyruvate dehydrogenase kinase activity drives metabolic heterogeneity and tumorigenesis in the intestine | Mus musculus | Massachusetts General Hospital | MS | 2022-02-16 | 1 | 3 | Uploaded data (6.2G)* |
