Down-regulation of β-catenin TCF signaling is linked to colonic epithelial cell differentiation

J. M. Mariadason, M. Bordonaro, F. Aslam, L. Shi, M. Kuraguchi, A. Velcich, Leonard H. Augenlicht

Research output: Contribution to journalArticle

155 Citations (Scopus)

Abstract

The β-catenin TCF pathway is implicated in the regulation of colonic epithelial cell proliferation, but its role in the regulation of cell differentiation is unknown. The colon carcinoma cell line, Caco-2, spontaneously undergoes Go/G1 cell cycle arrest and differentiates along the absorptive cell lineage over 21 days in culture. In parallel, we show that β-catenin-TCF activity and complex formation are significantly down-regulated. The down-regulation of β-catenin-TCF signaling was independent of APC, which we characterized as having a nonsense mutation in codon 1367 in Caco-2 cells, but was associated with a decrease in TCF-4 protein levels. Total β-catenin levels increased during Caco-2 cell differentiation, although this was attributable to an increase in the membrane, E-cadherin-associated, fraction of β-catenin. Importantly, down-regulation of β-catenin-TCF signaling in undifferentiated Caco-2 cells by three different mechanisms, ectopic expression of E-cadherin, wild-type APC, or dominant negative TCF-4, resulted in an increase in the promoter activities of two genes that are well-established markers of cell differentiation, alkaline phosphatase and intestinal fatty acid binding protein. These studies demonstrate, therefore, that in addition to its established role in the regulation of cell proliferation, down-regulation of the β-catenin-TCF pathway is associated with the promotion of a more-differentiated phenotype in colonic epithelial cells.

Original languageEnglish (US)
Pages (from-to)3465-3471
Number of pages7
JournalCancer Research
Volume61
Issue number8
StatePublished - Apr 15 2001

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Catenins
Cell Differentiation
Down-Regulation
Epithelial Cells
Caco-2 Cells
Cadherins
Cell Proliferation
G1 Phase Cell Cycle Checkpoints
Fatty Acid-Binding Proteins
Nonsense Codon
Cell Lineage
Codon
Alkaline Phosphatase
Colon
Carcinoma
Phenotype
Cell Line
Membranes
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Mariadason, J. M., Bordonaro, M., Aslam, F., Shi, L., Kuraguchi, M., Velcich, A., & Augenlicht, L. H. (2001). Down-regulation of β-catenin TCF signaling is linked to colonic epithelial cell differentiation. Cancer Research, 61(8), 3465-3471.

Down-regulation of β-catenin TCF signaling is linked to colonic epithelial cell differentiation. / Mariadason, J. M.; Bordonaro, M.; Aslam, F.; Shi, L.; Kuraguchi, M.; Velcich, A.; Augenlicht, Leonard H.

In: Cancer Research, Vol. 61, No. 8, 15.04.2001, p. 3465-3471.

Research output: Contribution to journalArticle

Mariadason, JM, Bordonaro, M, Aslam, F, Shi, L, Kuraguchi, M, Velcich, A & Augenlicht, LH 2001, 'Down-regulation of β-catenin TCF signaling is linked to colonic epithelial cell differentiation', Cancer Research, vol. 61, no. 8, pp. 3465-3471.
Mariadason JM, Bordonaro M, Aslam F, Shi L, Kuraguchi M, Velcich A et al. Down-regulation of β-catenin TCF signaling is linked to colonic epithelial cell differentiation. Cancer Research. 2001 Apr 15;61(8):3465-3471.
Mariadason, J. M. ; Bordonaro, M. ; Aslam, F. ; Shi, L. ; Kuraguchi, M. ; Velcich, A. ; Augenlicht, Leonard H. / Down-regulation of β-catenin TCF signaling is linked to colonic epithelial cell differentiation. In: Cancer Research. 2001 ; Vol. 61, No. 8. pp. 3465-3471.
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