β-catenin—A Linchpin in Colorectal Carcinogenesis?

NACS Wong, M Pignatelli - The American journal of pathology, 2002 - Elsevier
NACS Wong, M Pignatelli
The American journal of pathology, 2002Elsevier
An important role for β-catenin pathways in colorectal carcinogenesis was first suggested by
the protein's association with adenomatous polyposis coli (APC) protein, and by evidence of
dysregulation of β-catenin protein expression at all stages of the adenoma-carcinoma
sequence. Recent studies have, however, shown that yet more components of colorectal
carcinogenesis are linked to β-catenin pathways. Pro-oncogenic factors that also release β-
catenin from the adherens complex and/or encourage translocation to the nucleus include …
An important role for β-catenin pathways in colorectal carcinogenesis was first suggested by the protein's association with adenomatous polyposis coli (APC) protein, and by evidence of dysregulation of β-catenin protein expression at all stages of the adenoma-carcinoma sequence. Recent studies have, however, shown that yet more components of colorectal carcinogenesis are linked to β-catenin pathways. Pro-oncogenic factors that also release β-catenin from the adherens complex and/or encourage translocation to the nucleus include ras, epidermal growth factor (EGF), c-erbB-2, PKC-βII, MUC1, and PPAR-γ, whereas anti-oncogenic factors that also inhibit nuclear β-catenin signaling include transforming growth factor (TGF)-β, retinoic acid, and vitamin D. Association of nuclear β-catenin with the T cell factor (TCF)/lymphoid enhancer factor (LEF) family of transcription factors promotes the expression of several compounds that have important roles in the development and progression of colorectal carcinoma, namely: c-myc, cyclin D1, gastrin, cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-7, urokinase-type plasminogen activator receptor (aPAR), CD44 proteins, and P-glycoprotein. Finally, genetic aberrations of several components of the β-catenin pathways, eg, Frizzled (Frz), AXIN, and TCF-4, may potentially contribute to colorectal carcinogenesis. In discussing the above interactions, this review demonstrates that β-catenin represents a key molecule in the development of colorectal carcinoma.
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