scholarly journals Adenomatous Polyposis Coli Tumor Suppressor Protein Has Signaling Activity in Xenopus laevis Embryos Resulting in the Induction of an Ectopic Dorsoanterior Axis

1997 ◽  
Vol 136 (2) ◽  
pp. 411-420 ◽  
Author(s):  
Kris Vleminckx ◽  
Ellen Wong ◽  
Kathy Guger ◽  
Bonnee Rubinfeld ◽  
Paul Polakis ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Tumor Suppressor ◽  
Adenomatous Polyposis Coli ◽  
Protein A ◽  
Homeobox Gene ◽  
Xenopus Embryo ◽  
Adenomatous Polyposis ◽  
Polyposis Coli ◽  
Human Colon Cancer ◽  
Signaling Activity

Mutations in the adenomatous polyposis coli (APC) tumor suppressor gene are linked to both familial and sporadic human colon cancer. So far, a clear biological function for the APC gene product has not been determined. We assayed the activity of APC in the early Xenopus embryo, which has been established as a good model for the analysis of the signaling activity of the APC-associated protein β-catenin. When expressed in the future ventral side of a four-cell embryo, full-length APC induced a secondary dorsoanterior axis and the induction of the homeobox gene Siamois. This is similar to the phenotype previously observed for ectopic β-catenin expression. In fact, axis induction by APC required the availability of cytosolic β-catenin. These results indicate that APC has signaling activity in the early Xenopus embryo. Signaling activity resides in the central domain of the protein, a part of the molecule that is missing in most of the truncating APC mutations in colon cancer. Signaling by APC in Xenopus embryos is not accompanied by detectable changes in expression levels of β-catenin, indicating that it has direct positive signaling activity in addition to its role in β-catenin turnover. From these results we propose a model in which APC acts as part of the Wnt/β-catenin signaling pathway, either upstream of, or in conjunction with, β-catenin.

scholarly journals Regulation of Wnt signaling by the tumor suppressor adenomatous polyposis coli does not require the ability to enter the nucleus or a particular cytoplasmic localization

2012 ◽  
Vol 23 (11) ◽  
pp. 2041-2056 ◽  
Author(s):  
David M. Roberts ◽  
Mira I. Pronobis ◽  
John S. Poulton ◽  
Eric G. Kane ◽  
Mark Peifer
Keyword(s):  
Colon Cancer ◽  
Tumor Suppressor ◽  
Wnt Signaling ◽  
Cancer Cells ◽  
Adenomatous Polyposis Coli ◽  
Subcellular Location ◽  
Adenomatous Polyposis ◽  
Colon Cancer Cells ◽  
Polyposis Coli ◽  
Drosophila Embryos

Wnt signaling plays key roles in development and disease. The tumor suppressor adenomatous polyposis coli (APC) is an essential negative regulator of Wnt signaling. Its best-characterized role is as part of the destruction complex, targeting the Wnt effector β-catenin (βcat) for phosphorylation and ultimate destruction, but several studies suggested APC also may act in the nucleus at promoters of Wnt-responsive genes or to shuttle βcat out for destruction. Even in its role in the destruction complex, APC's mechanism of action remains mysterious. We have suggested APC positions the destruction complex at the appropriate subcellular location, facilitating βcat destruction. In this study, we directly tested APC's proposed roles in the nucleus or in precisely localizing the destruction complex by generating a series of APC2 variants to which we added tags relocalizing otherwise wild-type APC to different cytoplasmic locations. We tested these for function in human colon cancer cells and Drosophila embryos. Strikingly, all rescue Wnt regulation and down-regulate Wnt target genes in colon cancer cells, and most restore Wnt regulation in Drosophila embryos null for both fly APCs. These data suggest that APC2 does not have to shuttle into the nucleus or localize to a particular subcellular location to regulate Wnt signaling.

scholarly journals Original CIN: reviewing roles for APC in chromosome instability

2008 ◽  
Vol 181 (5) ◽  
pp. 719-726 ◽  
Author(s):  
Nasser M. Rusan ◽  
Mark Peifer
Keyword(s):  
Colon Cancer ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Adenomatous Polyposis Coli ◽  
Chromosome Instability ◽  
Original Sin ◽  
Adenomatous Polyposis ◽  
Colon Cancer Cells ◽  
Polyposis Coli ◽  
Bumper Sticker

You may have seen the bumper sticker “Eve was framed.” Thousands of years of being blamed for original sin and still many wonder, where's the evidence? Today, the tumor suppressor adenomatous polyposis coli (APC) may have the same complaint about accusations of a different type of CIN, chromosome instability. A series of recent papers, including three in this journal, propose that loss of APC function plays an important role in the CIN seen in many colon cancer cells. However, a closer look reveals a complex story that raises more questions than answers.

Biology of the Adenomatous Polyposis Coli Tumor Suppressor

2000 ◽  
Vol 18 (9) ◽  
pp. 1967-1979 ◽  
Author(s):  
Kathleen Heppner Goss ◽  
Joanna Groden
Keyword(s):  
Colon Cancer ◽  
Tumor Suppressor ◽  
Adenomatous Polyposis Coli ◽  
Cancer Progression ◽  
Apc Gene ◽  
Colorectal Adenomas ◽  
Beta Catenin ◽  
Adenomatous Polyposis ◽  
Polyposis Coli ◽  
Familial Adenomatous Polyposis Coli

ABSTRACT: The adenomatous polyposis coli (APC) gene was first identified as the gene mutated in an inherited syndrome of colon cancer predisposition known as familial adenomatous polyposis coli (FAP). Mutation of APC is also found in 80% of all colorectal adenomas and carcinomas and is one of the earliest mutations in colon cancer progression. Similar to other tumor suppressor genes, both APC alleles are inactivated by mutation in colon tumors, resulting in the loss of full-length protein in tumor cells. The functional significance of altering APC is the dysregulation of several physiologic processes that govern colonic epithelial cell homeostasis, which include cell cycle progression, migration, differentiation, and apoptosis. Roles for APC in some of these processes are in large part attributable to its ability to regulate cytosolic levels of the signaling molecule beta-catenin and to affect the transcriptional profile in cells. This article summarizes numerous genetic, biochemical, and cell biologic studies on the mechanisms of APC-mediated tumor suppression. Mouse models of FAP, in which the APC gene has been genetically inactivated, have been particularly useful in testing therapeutic and chemopreventive strategies. These data have significant implications for colorectal cancer treatment approaches as well as for understanding other disease genes and cancers of other tissue types.

scholarly journals Genes regulating membrane-associated E-cadherin and proliferation in adenomatous polyposis coli mutant colon cancer cells: High content siRNA screen

PLoS ONE ◽  
2020 ◽  
Vol 15 (10) ◽  
pp. e0240746
Author(s):  
Lauren E. King ◽  
Hui-Hua Zhang ◽  
Cathryn M. Gould ◽  
Daniel W. Thomas ◽  
Lachlan W. Whitehead ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Adenomatous Polyposis Coli ◽  
Adenomatous Polyposis ◽  
Colon Cancer Cells ◽  
Polyposis Coli ◽  
Sirna Screen ◽  
Coli Mutant ◽  
E Cadherin
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