TY - JOUR
T1 - Interaction of nuclear receptors with the Wnt/β-catenin/Tcf signaling axis
T2 - Wnt you like to know?
AU - Mulholland, David J.
AU - Dedhar, Shoukat
AU - Coetzee, Gerhard A.
AU - Nelson, Colleen C.
PY - 2005/12
Y1 - 2005/12
N2 - The cross-regulation of Wnt/β-catenin/Tcf ligands, kinases, and transcription factors with members of the nuclear receptor (NR) family has emerged as a clinically and developmentally important area of endocrine cell biology. Interactions between these signaling pathways result in a diverse array of cellular effects including altered cellular adhesion, tissue morphogenesis, and oncogenesis. Analyses of NR interactions with canonical Wnt signaling reveal two broad themes: Wnt/β-catenin modulation of NRs (theme I), and ligand-dependent NR inhibition of the Wnt/β-catenin/Tcf cascade (theme II). β-Catenin, a promiscuous Wnt signaling member, has been studied intensively in relation to the androgen receptor (AR). β-Catenin acts as a coactivator of AR transcription and is also involved in cotrafficking, increasing cell proliferation, and prostate pathogenesis. T cell factor, a transcriptional mediator of β-catenin and AR, engages in a dynamic reciprocity of nuclear β-catenin, p300/CREB binding protein, and transcriptional initiation factor 2/GC receptor-interaction protein, thereby facilitating hormone-dependent coactivation and transrepression. β-Catenin responds in an equally dynamic manner with other NRs, including the retinoic acid (RA) receptor (RAR), vitamin D receptor (VDR), glucocorticoid receptor (GR), progesterone receptor, thyroid receptor (TR), estrogen receptor (ER), and peroxisome proliferator-activated receptor (PPAR). The NR ligands, vitamin D3, trans/cis RA, glucocorticoids, and thiazolidines, induce dramatic changes in the physiology of cells harboring high Wnt/β-catenin/Tcf activity. Wnt signaling regulates, directly or indirectly, developmental processes such as ductal branching and adipogenesis, two processes dependent on NR function. β-Catenin has been intensively studied in colorectal cancer; however, it is now evident that β-catenin may be important in cancers of the breast, prostate, and thyroid. This review will focus on the cross-regulation of AR and Wnt/β-catenin/Tcf but will also consider the dynamic manner in which RAR/RXR, GR, TR, VDR, ER, and PPAR modulate canonical Wnt signaling. Although many commonalities exist by which NRs interact with the Wnt/β-catenin signaling pathway, striking cell line and tissue-specific differences require deciphering and application to endocrine pathology.
AB - The cross-regulation of Wnt/β-catenin/Tcf ligands, kinases, and transcription factors with members of the nuclear receptor (NR) family has emerged as a clinically and developmentally important area of endocrine cell biology. Interactions between these signaling pathways result in a diverse array of cellular effects including altered cellular adhesion, tissue morphogenesis, and oncogenesis. Analyses of NR interactions with canonical Wnt signaling reveal two broad themes: Wnt/β-catenin modulation of NRs (theme I), and ligand-dependent NR inhibition of the Wnt/β-catenin/Tcf cascade (theme II). β-Catenin, a promiscuous Wnt signaling member, has been studied intensively in relation to the androgen receptor (AR). β-Catenin acts as a coactivator of AR transcription and is also involved in cotrafficking, increasing cell proliferation, and prostate pathogenesis. T cell factor, a transcriptional mediator of β-catenin and AR, engages in a dynamic reciprocity of nuclear β-catenin, p300/CREB binding protein, and transcriptional initiation factor 2/GC receptor-interaction protein, thereby facilitating hormone-dependent coactivation and transrepression. β-Catenin responds in an equally dynamic manner with other NRs, including the retinoic acid (RA) receptor (RAR), vitamin D receptor (VDR), glucocorticoid receptor (GR), progesterone receptor, thyroid receptor (TR), estrogen receptor (ER), and peroxisome proliferator-activated receptor (PPAR). The NR ligands, vitamin D3, trans/cis RA, glucocorticoids, and thiazolidines, induce dramatic changes in the physiology of cells harboring high Wnt/β-catenin/Tcf activity. Wnt signaling regulates, directly or indirectly, developmental processes such as ductal branching and adipogenesis, two processes dependent on NR function. β-Catenin has been intensively studied in colorectal cancer; however, it is now evident that β-catenin may be important in cancers of the breast, prostate, and thyroid. This review will focus on the cross-regulation of AR and Wnt/β-catenin/Tcf but will also consider the dynamic manner in which RAR/RXR, GR, TR, VDR, ER, and PPAR modulate canonical Wnt signaling. Although many commonalities exist by which NRs interact with the Wnt/β-catenin signaling pathway, striking cell line and tissue-specific differences require deciphering and application to endocrine pathology.
UR - http://www.scopus.com/inward/record.url?scp=28844439793&partnerID=8YFLogxK
U2 - 10.1210/er.2003-0034
DO - 10.1210/er.2003-0034
M3 - Review article
C2 - 16126938
AN - SCOPUS:28844439793
SN - 0163-769X
VL - 26
SP - 898
EP - 915
JO - Endocrine Reviews
JF - Endocrine Reviews
IS - 7
ER -