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Cited by 106Wnt/β-catenin signaling in development and cancerGenetic factors in colorectal cancerSignaling Pathways in Disease

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Lymphoid enhancer factor/T cell factor expression in colorectal cancer

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Waterman, Marian L.·2004·Cancer and Metastasis Reviews
DOI 10.1023/a:1025858928620
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Abstract

Genetic inactivation of key components of the Wnt signal transduction system is a frequent event in colorectal cancer. These genetic mutations lead to stabilization of beta-catenin, a cytoplasmic-nuclear shuttling protein with a potent transcription activation domain. Stabilization and subsequent nuclear localization of beta-catenin produces aberrant, Wnt-independent signals to target genes, an activity tightly linked to the genesis of colon cancers. In the nucleus, the transcription factor family of LEF/TCF proteins transmits Wnt signals by binding to beta-catenin and recruiting it to target genes for activation. Such activities are carried out by full-length LEF/TCFs that are thought to be mostly interchangeable and redundant. However, truncated forms of LEF-1 and TCF-1 that do not bind to beta-catenin function as dominant negatives and an alternatively spliced TCF isoform with a unique activation function has recently been discovered. The dominant negative forms block Wnt signals because they occupy Wnt target genes and limit beta-catenin access; the alternatively spliced TCF isoform activates certain Wnt target promoters whereas other TCF isoforms and LEF-1 do not. A study of LEF/TCF expression and activity in normal intestine and colon carcinomas suggests that the relative amounts of LEF/TCF isoforms may change as tumors progress and this may influence the strength and specificity of Wnt signals in the nucleus. While the underlying mechanism for a change in the LEF/TCF isoform expression is not yet known, recent evidence implicates the Wnt signaling pathway itself as a potential modulator.

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Metadata

Authors
Waterman, M. L.
Affiliations
University of California, Irvine (US)
Corresponding author
Waterman, Marian L.
ORCID
Waterman, Marian L.
Venue
Cancer and Metastasis Reviews
Publisher
Springer Science and Business Media LLC
Published
2004-01
Volume
23
Issue
1-2
Pages
41-52
ISSN
  • 0167-7659 (ISSN-L)
  • 1573-7233
DOI
10.1023/a:1025858928620
OpenAlex
W2022623685
Cited by
106
References
4
Citations by year
2026: 1 · 2025: 2 · 2024: 1 · 2023: 4 · 2022: 1 · 2021: 7 · 2020: 3 · 2019: 3 · 2018: 2 · 2017: 5 · 2016: 2 · 2015: 3 · 2014: 9 · 2013: 9 · 2012: 6
FWCI
0.26
Type
journal article
Language
en
Open access
Licence
Locations
  • Cancer and Metastasis Reviews (publishedVersion)
  • PubMed (publishedVersion)
  • Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, cc-by-sa)
Funders
National Cancer Institute (CA096878, R01CA096878, CA8392)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Keywords
T-cell factor, colorectal cancer, Wnt signaling, β-catenin stabilization, LEF1, TCF1, dominant-negative isoform, alternative splicing, transcription factor isoforms, tumor progression, colon cancer
MeSH terms
Cell Nucleus, DNA-Binding Proteins, Exons, Genes, Dominant, Humans, Models, Biological, Models, Genetic, Promoter Regions, Genetic, Protein Binding, Transcription Factors, Colorectal Neoplasms, Signal Transduction, Protein Structure, Tertiary, Protein Isoforms, Lymphoid Enhancer-Binding Factor 1, T Cell Transcription Factor 1

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