Research ArticleCancer

β-Catenin Promotes Colitis and Colon Cancer Through Imprinting of Proinflammatory Properties in T Cells

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Science Translational Medicine  26 Feb 2014:
Vol. 6, Issue 225, pp. 225ra28
DOI: 10.1126/scitranslmed.3007607

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β-Catenin, Corrupter of the Tregs

It is well known that the numbers and types of lymphocytes that infiltrate colon tumors are relevant to the clinical outcome. However, the reasons for this association are complex and not yet fully understood. Here, Keerthivasan and colleagues identify β-catenin as a culprit and show that it directly contributes to inflammation and colon carcinogenesis in patients and mice with underlying colitis.

Keerthivasan and coauthors also provide a mechanistic explanation for the observed effects, showing that the expression of β-catenin in T cells induces the expression of T helper 17 (TH17) genes. This activation of TH17 genes converts T cells to a proinflammatory phenotype and impairs Treg development. Mice overexpressing β-catenin all develop colitis and then colitis-induced cancer, even when the β-catenin is overexpressed only in Tregs. Similarly, human patients with colitis-induced or sporadic colon cancer have abnormally high amounts of β-catenin–expressing T cells in their tumors, confirming the relevance of the mouse findings to human disease.