Cancer and Metastasis Reviews

, Volume 23, Issue 1, pp 41–52

Lymphoid enhancer factor/T cell factor expression in colorectal cancer

  • Marian L. Waterman

DOI: 10.1023/A:1025858928620

Cite this article as:
Waterman, M.L. Cancer Metastasis Rev (2004) 23: 41. doi:10.1023/A:1025858928620


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 β-catenin, a cytoplasmic–nuclear shuttling protein with a potent transcription activation domain. Stabilization and subsequent nuclear localization of β-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 β-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 β-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 β-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.


Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • Marian L. Waterman
    • 1
  1. 1.Department of Microbiology and Molecular Genetics, College of MedicineUniversity of California, IrvineIrvineUSA