WNT and cyclooxygenase-2 cross-talk accelerates adenoma growth

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

Research output: Contribution to journalArticle

41 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1512-1515
Number of pages4
JournalCell Cycle
Volume3
Issue number12
StatePublished - Dec 2004
Externally publishedYes

Fingerprint

Peroxisome Proliferator-Activated Receptors
Cyclooxygenase 2
Adenoma
Growth
Colorectal Neoplasms
Artificial Receptors
Chromosomal Instability
Wnt Signaling Pathway
Dyslipidemias
Dinoprostone
Prostaglandins
Tumors
Obesity
Chemical activation
Neoplasms

Keywords

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

ASJC Scopus subject areas

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Cite this

Wang, D., Mann, J. R., & DuBois, R. N. (2004). WNT and cyclooxygenase-2 cross-talk accelerates adenoma growth. Cell Cycle, 3(12), 1512-1515.

WNT and cyclooxygenase-2 cross-talk accelerates adenoma growth. / Wang, Dingzhi; Mann, Jason R.; DuBois, Raymond N.

In: Cell Cycle, Vol. 3, No. 12, 12.2004, p. 1512-1515.

Research output: Contribution to journalArticle

Wang, D, Mann, JR & DuBois, RN 2004, 'WNT and cyclooxygenase-2 cross-talk accelerates adenoma growth', Cell Cycle, vol. 3, no. 12, pp. 1512-1515.
Wang D, Mann JR, DuBois RN. WNT and cyclooxygenase-2 cross-talk accelerates adenoma growth. Cell Cycle. 2004 Dec;3(12):1512-1515.
Wang, Dingzhi ; Mann, Jason R. ; DuBois, Raymond N. / WNT and cyclooxygenase-2 cross-talk accelerates adenoma growth. In: Cell Cycle. 2004 ; Vol. 3, No. 12. pp. 1512-1515.
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