Accession Number:

ADA614181

Title:

Role of SIRT6 in Metabolic Reprogramming During Colorectal Carcinoma

Descriptive Note:

Annual rept. 1 Sep 2013-31 Aug 2014

Corporate Author:

MASSACHUSETTS GENERAL HOSPITAL BOSTON

Personal Author(s):

Report Date:

2014-09-01

Pagination or Media Count:

66.0

Abstract:

During the research period stated above, we have expanded our colony of SIRT6 FF Villin- Cre APCmin mice and found that lack of SIRT6 dramatically increases intestinal tumorigenesis in vivo, and this phenotype is driven by an enhanced aerobic glycolysis in the absence of SIRT6. To study in more detail how SIRT6 and aerobic glycolysis modulates intestinal tumorigenesis, we have knocked-down SIRT6 in a panel of human CRC cell lines HCT116, SW620, HT29, SW1116. However, no differences in glycolytic metabolism were found. Alternatively, we have taken advantage of our mouse model and found that lack of SIRT6 leads to an increase in the number of intestinal stem cells ISC, suggesting that SIRT6 regulates intestinal tumorigenesis by controlling the number of tumor initiating cells. We have confirmed this result by using intestinal organoids derived from our mouse model. In parallel, we generated a SIRT6 FF, Lgr5-EGFP-Cre APCmin mouse line to precisely address the role of SIRT6 in the ISCs. Our preliminary data shows that SIRT6 FF, Lgr5-EGFP-Cre APCmin mice have increased numbers of ISCs compared to control animals, suggesting that SIRT6 might regulate ISC.

Subject Categories:

  • Biochemistry
  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE