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

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Imelda T Sandoval ◽  
Richard Glenn C Delacruz ◽  
Braden N Miller ◽  
Shauna Hill ◽  
Kristofor A Olson ◽  
...  
Keyword(s):  
Cell Fate ◽  
Adenomatous Polyposis Coli ◽  
Normal Development ◽  
Intestinal Cell ◽  
Adenomatous Polyposis ◽  
Polyposis Coli ◽  
Pyruvate Metabolism ◽  
Metabolic Switch ◽  
Intestinal Differentiation ◽  
Mitochondrial Pyruvate Carrier

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.

scholarly journals Author response: A metabolic switch controls intestinal differentiation downstream of Adenomatous polyposis coli (APC)

2017 ◽  
Author(s):  
Imelda T Sandoval ◽  
Richard Glenn C Delacruz ◽  
Braden N Miller ◽  
Shauna Hill ◽  
Kristofor A Olson ◽  
...  
Keyword(s):  
Adenomatous Polyposis Coli ◽  
Author Response ◽  
Adenomatous Polyposis ◽  
Polyposis Coli ◽  
Metabolic Switch ◽  
Intestinal Differentiation

scholarly journals Adenomatous Polyposis Coli (APC) Is Required for Normal Development of Skin and Thymus

PLoS Genetics ◽  
2006 ◽  
Vol 2 (9) ◽  
pp. e146 ◽  
Author(s):  
Mari Kuraguchi ◽  
Xiu-Ping Wang ◽  
Roderick T Bronson ◽  
Rebecca Rothenberg ◽  
Nana Yaw Ohene-Baah ◽  
...  
Keyword(s):  
Adenomatous Polyposis Coli ◽  
Normal Development ◽  
Adenomatous Polyposis ◽  
Polyposis Coli

scholarly journals Adenomatous polyposis coli protein (APC)-independent regulation of β-catenin/Tcf-4 mediated transcription in intestinal cells

1999 ◽  
Vol 344 (2) ◽  
pp. 565-570 ◽  
Author(s):  
Josep BAULIDA ◽  
Eduard BATLLE ◽  
Antonio GARCÍA DE HERREROS
Keyword(s):  
Adenomatous Polyposis Coli ◽  
Transcriptional Activity ◽  
Intestinal Cell ◽  
Adenomatous Polyposis ◽  
Polyposis Coli ◽  
Binding Assays ◽  
Adenomatous Polyposis Coli Protein ◽  
Kinase C ◽  
Intestinal Cell Lines

Alterations in the transcriptional activity of the β-catenin-Tcf complex have been associated with the earlier stages of colonic transformation. We show here that the activation of protein kinase C by the phorbol ester PMA in several intestinal cell lines increases the levels of β-catenin detected in the nucleus and augments the transcriptional activity mediated by β-catenin. The response to PMA was not related to modifications in the cytosolic levels of β-catenin and was observed not only in cells with wild-type adenomatous polyposis coli protein (APC) but also in APC-deficient cells. Binding assays in vitro revealed that PMA facilitates the interaction of the β-catenin with the nuclear structure. Our results therefore show that β-catenin-mediated transcription can be regulated independently of the presence of APC.

scholarly journals Adenomatous polyposis coli (APC) is required for normal development of skin and thymus

PLoS Genetics ◽  
2005 ◽  
Vol preprint (2006) ◽  
pp. e146
Author(s):  
Mari Kuraguchi ◽  
Xiu-Ping Wang ◽  
Roderick T Bronson ◽  
Rebecca Rothenberg ◽  
Nana Yaw Ohene-Baah ◽  
...  
Keyword(s):  
Adenomatous Polyposis Coli ◽  
Normal Development ◽  
Adenomatous Polyposis ◽  
Polyposis Coli
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