PUBLICATION
A metabolic switch controls intestinal differentiation downstream of Adenomatous polyposis coli (APC).
- Authors
- Sandoval, I.T., Delacruz, R.G., Miller, B.N., Hill, S., Olson, K.A., Gabriel, A.E., Boyd, K., Satterfield, C., Remmen, H.V., Rutter, J., Jones, D.A.
- ID
- ZDB-PUB-170412-6
- Date
- 2017
- Source
- eLIFE 6: (Journal)
- Registered Authors
- Keywords
- adenomatous polyposis coli, cancer biology, developmental biology, intestinal differentiation, mitochondrial pyruvate carrier, pyruvate metabolism, stem cells, zebrafish
- MeSH Terms
-
- Adenomatous Polyposis Coli Protein/deficiency
- Adenomatous Polyposis Coli Protein/genetics*
- Animals
- Carcinogenesis*
- Gene Expression Regulation*
- Humans
- Intestines/physiology*
- Metabolic Networks and Pathways
- Mitochondrial Membrane Transport Proteins/genetics*
- Models, Animal
- Pyruvic Acid/metabolism*
- Zebrafish
- PubMed
- 28397687 Full text @ Elife
Citation
Sandoval, I.T., Delacruz, R.G., Miller, B.N., Hill, S., Olson, K.A., Gabriel, A.E., Boyd, K., Satterfield, C., Remmen, H.V., Rutter, J., Jones, D.A. (2017) A metabolic switch controls intestinal differentiation downstream of Adenomatous polyposis coli (APC).. eLIFE. 6.
Abstract
Elucidating signaling pathways that regulate cellular metabolism is essential for a better understanding of normal development and tumorigenesis. Recent studies have shown that mitochondrial pyruvate carrier 1 (MPC1), a crucial player in pyruvate metabolism, is downregulated in colon adenocarcinomas. Utilizing zebrafish to examine the genetic relationship between MPC1 and Adenomatous polyposis coli (APC), a key tumor suppressor in colorectal cancer, we found that apc controls the levels of mpc1 and that knock down of mpc1 recapitulates phenotypes of impaired apc function including failed intestinal differentiation. Exogenous human MPC1 RNA rescued failed intestinal differentiation in zebrafish models of apc deficiency. Our data demonstrate a novel role for apc in pyruvate metabolism and that pyruvate metabolism dictates intestinal cell fate and differentiation decisions downstream of apc.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping