|ZFIN ID: ZDB-PUB-170412-6|
Your Input Welcome
Thank you for submitting comments. Your input has been emailed to ZFIN curators who may contact you if additional information is required.
Oops. Something went wrong. Please try again later.
A metabolic switch controls intestinal differentiation downstream of Adenomatous polyposis coli (APC).
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.
|Source:||eLIFE 6: (Journal)|
|Keywords:||adenomatous polyposis coli, cancer biology, developmental biology, intestinal differentiation, mitochondrial pyruvate carrier, pyruvate metabolism, stem cells, zebrafish|
|PubMed:||28397687 Full text @ Elife|
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.
ABSTRACTElucidating 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.