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PMID: 22155636 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Dysregulation of Wnt/β-catenin signaling in gastrointestinal cancers.

Gastroenterology ·Vol. 142 ·No. 2 ·2012-02-00 ·Pages 219-32

White BD, Chien AJ, Dawson DW

Abstract

Aberrant Wnt/β-catenin signaling is widely implicated in numerous malignancies, including cancers of the gastrointestinal tract. Dysregulation of signaling is traditionally attributed to mutations in Axin, adenomatous polyposis coli, and β-catenin that lead to constitutive hyperactivation of the pathway. However, Wnt/β-catenin signaling is also modulated through various other mechanisms in cancer, including cross talk with other altered signaling pathways. A more complex view of Wnt/β-catenin signaling and its role in gastrointestinal cancers is now emerging as divergent phenotypic outcomes are found to be dictated by temporospatial context and relative levels of pathway activation. This review summarizes the dysregulation of Wnt/β-catenin signaling in colorectal carcinoma, hepatocellular carcinoma, and pancreatic ductal adenocarcinoma, with particular emphasis on the latter two. We conclude by addressing some of the major challenges faced in attempting to target the pathway in the clinic.

MeSH Terms
Adenocarcinoma/genetics,metabolism Biomarkers, Tumor/genetics,metabolism Gastrointestinal Neoplasms/genetics,metabolism Humans Liver Neoplasms/genetics,metabolism Pancreatic Neoplasms/genetics,metabolism Wnt Proteins/genetics,metabolism Wnt Signaling Pathway/genetics,physiology beta Catenin/genetics,metabolism
Chemicals
Biomarkers, Tumor Wnt Proteins beta Catenin
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
White Bryan D
Science and Technology Program, University of Washington Bothell, Bothell, Washington, USA. bdwhite@u.washington.edu
Chien Andy J
Dawson David W
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Article Info
Journal
Gastroenterology
Abbr.
Gastroenterology
ISSN
1528-0012
DOI
10.1053/j.gastro.2011.12.001
Email
bdwhite@u.washington.edu
Published
2012-02-00
Epub
2011-00-08
Pages
219-32
Language
English
Region
United States
NLM ID
0374630
PMCID
PMC3285553
Subset
IM
Grants
NCI NIH HHS · K08 CA128565 · United States
NCI NIH HHS · K08 CA128565-01 · United States
NCI NIH HHS · 1K08CA128565 · United States
External Links
PubMed source DOI: 10.1053/j.gastro.2011.12.001 PMC Full Text View journal details
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