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Published on: October 11, 2019
Expression of lymphoid enhancer factor/T-cell factor proteins in colon cancer
1Department of Microbiology and Molecular Genetics, College of Medicine, University of California, Irvine, Irvine, California 92697, USA. mlwaterm@uci.edu
Abstract:
Molecular genetic analysis of colon cancers has established that the Wnt signaling pathway is involved in early tumor development. Mutation of midstream components can activate the pathway, making it independent of Wnt ligands and maintaining constant pressure to change target gene expression. The transcription factors that connect the pathway to target genes are members of the lymphoid enhancer factor/T-cell factor (LEF/TCF) family. The genes for two members of this family, TCF 7 and LEF 1, produce full-length forms that mediate Wnt signals and truncated dominant negative forms that limit Wnt signals and may function as growth suppressors. Results from studies of their expression in colon cancer suggests that because Wnt-linked cancers progress to malignancy, there may be a strengthening of the Wnt signal by selective expression of the activating forms of LEF/TCFs and a bias against suppressing, truncated forms.
Insights
Colon cancer progression involves the Wnt signaling pathway. Selective expression of activating lymphoid enhancer factor/T-cell factor (LEF/TCF) forms may drive tumor growth, while suppressing truncated forms are disfavored.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The Wnt signaling pathway is crucial in early colon tumor development.
- Mutations in Wnt pathway components can lead to ligand-independent activation, driving continuous target gene expression changes.
- Lymphoid enhancer factor/T-cell factor (LEF/TCF) transcription factors are key mediators connecting Wnt signals to target genes.
Purpose of the Study:
- To investigate the role of LEF/TCF family members in colon cancer progression.
- To understand how different forms of LEF/TCFs (full-length vs. truncated) contribute to Wnt signaling in malignancy.
Main Methods:
- Molecular genetic analysis of colon cancer tissues.
- Analysis of gene expression patterns for TCF7 and LEF1.
Main Results:
- The study suggests a shift in LEF/TCF expression during colon cancer progression.
- There appears to be selective expression of activating, full-length LEF/TCF forms.
- Expression of dominant-negative, truncated LEF/TCF forms, which may suppress growth, seems to be reduced.
Conclusions:
- Wnt signaling plays a significant role in the malignancy of colon cancers.
- The observed expression bias towards activating LEF/TCF forms may strengthen the Wnt signal.
- A reduced presence of growth-suppressing truncated LEF/TCF forms could contribute to tumor progression.
