WNT and cyclooxygenase-2 cross-talk accelerates adenoma growth

Dingzhi Wang; Jason R. Mann; Raymond N. DuBois

doi:10.4161/cc.3.12.1288

WNT and cyclooxygenase-2 cross-talk accelerates adenoma growth

Dingzhi Wang, Jason R. Mann, Raymond N. DuBois

Research output: Contribution to journal › Review article › peer-review

44 Scopus citations

Abstract

Both Wnt and cyclooxygenase (COX)-2 pathways are activated in most sporadic and familial colorectal cancers, especially in those with chromosomal instability. We have recently shown that a common target of both signaling pathways, the peroxisome proliferator-activated receptor (PPAR)-δ, is involved in intestinal adenoma growth. Activation of this receptor by synthetic agonist (GW501516) or COX-2-derived prostaglandin E₂ (PGE ₂) accelerates intestinal adenoma growth in Apc^Min mice. Moreover, these effects are lost in Apc^Min mice lacking PPARδ. These findings implicate PPARδ as a focal point of cross-talk between the Wnt and prostaglandin signaling pathways. Based on this work it looks as if PPARδ agonists currently in development for treatment of dyslipidemias and obesity may increase the risk of tumor formation in humans. By contrast, antagonists of PPARδ may provide a novel approach for prevention and treatment of colorectal cancer.

Original language	English (US)
Pages (from-to)	1512-1515
Number of pages	4
Journal	Cell Cycle
Volume	3
Issue number	12
DOIs	https://doi.org/10.4161/cc.3.12.1288
State	Published - Dec 2004
Externally published	Yes

Keywords

Adenomatous polyposis coli
Colorectal cancer
Cyclooxygenase-2
Peroxisome proliferator-activated receptor δ
Prostaglandin E2
β-catenin

ASJC Scopus subject areas

Molecular Biology
Developmental Biology
Cell Biology

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10.4161/cc.3.12.1288

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title = "WNT and cyclooxygenase-2 cross-talk accelerates adenoma growth",

abstract = "Both Wnt and cyclooxygenase (COX)-2 pathways are activated in most sporadic and familial colorectal cancers, especially in those with chromosomal instability. We have recently shown that a common target of both signaling pathways, the peroxisome proliferator-activated receptor (PPAR)-δ, is involved in intestinal adenoma growth. Activation of this receptor by synthetic agonist (GW501516) or COX-2-derived prostaglandin E2 (PGE 2) accelerates intestinal adenoma growth in ApcMin mice. Moreover, these effects are lost in ApcMin mice lacking PPARδ. These findings implicate PPARδ as a focal point of cross-talk between the Wnt and prostaglandin signaling pathways. Based on this work it looks as if PPARδ agonists currently in development for treatment of dyslipidemias and obesity may increase the risk of tumor formation in humans. By contrast, antagonists of PPARδ may provide a novel approach for prevention and treatment of colorectal cancer.",

keywords = "Adenomatous polyposis coli, Colorectal cancer, Cyclooxygenase-2, Peroxisome proliferator-activated receptor δ, Prostaglandin E2, β-catenin",

author = "Dingzhi Wang and Mann, {Jason R.} and DuBois, {Raymond N.}",

note = "Funding Information: We acknowledge support from the United States Public Health Services Grants RO-DK-62112 and PO-CA77839. RND is the Hortense B. Ingram Professor of Molecular Oncology and the recipient of an NIH MERIT award (R37-DK47297). Funding Information: We also thank the T.J. Martell Foundation and the National Colorectal Cancer Research Alliance (NCCRA) for generous support.",

year = "2004",

month = dec,

doi = "10.4161/cc.3.12.1288",

language = "English (US)",

volume = "3",

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T1 - WNT and cyclooxygenase-2 cross-talk accelerates adenoma growth

AU - Wang, Dingzhi

AU - Mann, Jason R.

AU - DuBois, Raymond N.

N1 - Funding Information: We acknowledge support from the United States Public Health Services Grants RO-DK-62112 and PO-CA77839. RND is the Hortense B. Ingram Professor of Molecular Oncology and the recipient of an NIH MERIT award (R37-DK47297). Funding Information: We also thank the T.J. Martell Foundation and the National Colorectal Cancer Research Alliance (NCCRA) for generous support.

PY - 2004/12

Y1 - 2004/12

N2 - Both Wnt and cyclooxygenase (COX)-2 pathways are activated in most sporadic and familial colorectal cancers, especially in those with chromosomal instability. We have recently shown that a common target of both signaling pathways, the peroxisome proliferator-activated receptor (PPAR)-δ, is involved in intestinal adenoma growth. Activation of this receptor by synthetic agonist (GW501516) or COX-2-derived prostaglandin E2 (PGE 2) accelerates intestinal adenoma growth in ApcMin mice. Moreover, these effects are lost in ApcMin mice lacking PPARδ. These findings implicate PPARδ as a focal point of cross-talk between the Wnt and prostaglandin signaling pathways. Based on this work it looks as if PPARδ agonists currently in development for treatment of dyslipidemias and obesity may increase the risk of tumor formation in humans. By contrast, antagonists of PPARδ may provide a novel approach for prevention and treatment of colorectal cancer.

AB - Both Wnt and cyclooxygenase (COX)-2 pathways are activated in most sporadic and familial colorectal cancers, especially in those with chromosomal instability. We have recently shown that a common target of both signaling pathways, the peroxisome proliferator-activated receptor (PPAR)-δ, is involved in intestinal adenoma growth. Activation of this receptor by synthetic agonist (GW501516) or COX-2-derived prostaglandin E2 (PGE 2) accelerates intestinal adenoma growth in ApcMin mice. Moreover, these effects are lost in ApcMin mice lacking PPARδ. These findings implicate PPARδ as a focal point of cross-talk between the Wnt and prostaglandin signaling pathways. Based on this work it looks as if PPARδ agonists currently in development for treatment of dyslipidemias and obesity may increase the risk of tumor formation in humans. By contrast, antagonists of PPARδ may provide a novel approach for prevention and treatment of colorectal cancer.

KW - Adenomatous polyposis coli

KW - Colorectal cancer

KW - Cyclooxygenase-2

KW - Peroxisome proliferator-activated receptor δ

KW - Prostaglandin E2

KW - β-catenin

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ER -

WNT and cyclooxygenase-2 cross-talk accelerates adenoma growth

Abstract

Keywords

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