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A metabolic switch controls intestinal differentiation downstream of Adenomatous polyposis coli (APC).

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.

SUBMITTER: Sandoval IT 

PROVIDER: S-EPMC5388534 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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A metabolic switch controls intestinal differentiation downstream of <i>Adenomatous</i> polyposis coli (APC).

Sandoval Imelda T IT   Delacruz Richard Glenn C RG   Miller Braden N BN   Hill Shauna S   Olson Kristofor A KA   Gabriel Ana E AE   Boyd Kevin K   Satterfield Christeena C   Van Remmen Holly H   Rutter Jared J   Jones David A DA  

eLife 20170411

Elucidating signaling pathways that regulate cellular metabolism is essential for a better understanding of normal development and tumorigenesis. Recent studies have shown that <i>mitochondrial pyruvate carrier 1 (MPC1)</i>, a crucial player in pyruvate metabolism, is downregulated in colon adenocarcinomas. Utilizing zebrafish to examine the genetic relationship between <i>MPC1</i> and <i>Adenomatous polyposis coli (APC),</i> a key tumor suppressor in colorectal cancer, we found that <i>apc</i>  ...[more]

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