TY - JOUR
T1 - β-catenin - A linchpin in colorectal carcinogenesis?
AU - Wong, Newton Alexander Chiang Shuek
AU - Pignatelli, Massimo
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0036174452&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036174452&partnerID=8YFLogxK
U2 - 10.1016/S0002-9440(10)64856-0
DO - 10.1016/S0002-9440(10)64856-0
M3 - Review article
C2 - 11839557
AN - SCOPUS:0036174452
SN - 0002-9440
VL - 160
SP - 389
EP - 401
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 2
ER -