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

Imelda T. Sandoval, Richard Glenn C. Delacruz, Braden N. Miller, Shauna Hill, Kristofor A. Olson, Ana E. Gabriel, Kevin Boyd, Christeena Satterfield, Holly Van Remmen, Jared Rutter, David A. Jones

Research output: Contribution to journalArticle

13 Scopus citations

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.

Original languageEnglish (US)
Article numbere22706
JournaleLife
Volume6
DOIs
StatePublished - Apr 11 2017
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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    Sandoval, I. T., Delacruz, R. G. C., Miller, B. N., Hill, S., Olson, K. A., Gabriel, A. E., Boyd, K., Satterfield, C., Van Remmen, H., Rutter, J., & Jones, D. A. (2017). A metabolic switch controls intestinal differentiation downstream of adenomatous polyposis coli (APC). eLife, 6, [e22706]. https://doi.org/10.7554/eLife.22706