title: A metabolic switch controls intestinal differentiation downstream ofAdenomatouspolyposis 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 thatmitochondrial pyruvate carrier 1 (MPC1), a crucial player in pyruvate metabolism, is downregulated in colon adenocarcinomas. Utilizing zebrafish to examine the genetic relationship betweenMPC1andAdenomatous polyposis coli (APC),a key tumor suppressor in colorectal cancer, we found thatapccontrols the levels ofmpc1and that knock down ofmpc1recapitulates phenotypes of impairedapcfunction including failed intestinal differentiation. Exogenous humanMPC1 RNArescued failed intestinal differentiation in zebrafish models ofapcdeficiency. Our data demonstrate a novel role forapcin pyruvate metabolism and that pyruvate metabolism dictates intestinal cell fate and differentiation decisions downstream ofapc.
authors.affiliation: Functional and Chemical Genomics, Oklahoma Medical Research Foundation, Oklahoma City, United States.
authors.forename: Imelda T
authors.identifier: 0000-0002-5400-5611
authors.initials: IT
authors.lastname: Sandoval
authors.affiliation: Functional and Chemical Genomics, Oklahoma Medical Research Foundation, Oklahoma City, United States.
authors.forename: Richard Glenn C
authors.initials: RG
authors.lastname: Delacruz
authors.affiliation: Functional and Chemical Genomics, Oklahoma Medical Research Foundation, Oklahoma City, United States.
authors.forename: Braden N
authors.initials: BN
authors.lastname: Miller
authors.affiliation: Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, United States.|Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, United States.
authors.forename: Shauna
authors.initials: S
authors.lastname: Hill
authors.affiliation: Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States.
authors.forename: Kristofor A
authors.initials: KA
authors.lastname: Olson
authors.affiliation: Functional and Chemical Genomics, Oklahoma Medical Research Foundation, Oklahoma City, United States.
authors.forename: Ana E
authors.initials: AE
authors.lastname: Gabriel
authors.affiliation: Functional and Chemical Genomics, Oklahoma Medical Research Foundation, Oklahoma City, United States.
authors.forename: Kevin
authors.initials: K
authors.lastname: Boyd
authors.affiliation: Functional and Chemical Genomics, Oklahoma Medical Research Foundation, Oklahoma City, United States.
authors.forename: Christeena
authors.initials: C
authors.lastname: Satterfield
authors.affiliation: Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, United States.
authors.forename: Holly
authors.initials: H
authors.lastname: Van Remmen
authors.affiliation: Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States.
authors.forename: Jared
authors.identifier: 0000-0002-2710-9765
authors.initials: J
authors.lastname: Rutter
authors.affiliation: Functional and Chemical Genomics, Oklahoma Medical Research Foundation, Oklahoma City, United States.
authors.forename: David A
authors.identifier: 0000-0002-2391-779X
authors.initials: DA
authors.lastname: Jones
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000172:deficiency / Q000235:genetics*; D000818:Animals; D063646:Carcinogenesis; D005786:Gene Expression Regulation; D006801:Humans; D007422:Intestines / Q000502:physiology*; D053858:Metabolic Networks and Pathways; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics*; D023421:Models, Animal; D027501:Monocarboxylic Acid Transporters; D019289:Pyruvic Acid / Q000378:metabolism*; D015027:Zebrafish
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; C573718:MPC1 protein, human; D033681:Mitochondrial Membrane Transport Proteins; D027501:Monocarboxylic Acid Transporters; D019289:Pyruvic Acid
keywords: adenomatous polyposis coli; cancer biology; developmental biology; intestinal differentiation; mitochondrial pyruvate carrier; pyruvate metabolism; stem cells; zebrafish