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Accession Number:
AD1003394
Title:
Role of SIRT6 in Metabolic Reprogramming During Colorectal Carcinoma
Corporate Author:
The Massachusetts General Hospital Boston United States
Report Date:
2015-09-01
Abstract:
Data generated during this year has uncovered a role for SIRT6 as a critical regulator of ISC activity. Using two different mouse models as well as an in vitro intestinal organoid system, I have found that lack of SIRT6 increases the number and activity of ISCs, a phenotype that is reversed by inhibiting glycolysis, indicating that enhanced glycolytic metabolism in the absence of SIRT6 drives intestinal tumorigenesis by increasing the number of tumor-initiating cells. In addition, we have found that ISCs are more glycolytic than more differentiated intestinal epithelial cells, and increased glycolysis in these cells regulates their stemness. Taken together, these results are in agreement with a model in which SIRT6 regulates ISCs activity by controlling glucose metabolism and, when lost, increased glycolysis promotes ISC expansion and the generation of potential tumor-initiating cells.
Descriptive Note:
Technical Report,01 Sep 2014,31 Aug 2015
Pages:
0021
Distribution Statement:
Approved For Public Release;
File Size:
8.55MB
