Prostaglandin E2 promotes colorectal adenoma growth via transactivation of the nuclear peroxisome proliferator-activated receptor δ

Dingzhi Wang, Haibin Wang, Qiong Shi, Sharada Katkuri, Walter Walhi, Beatrice Desvergne, Sanjoy K. Das, Sudhansu K. Dey, Raymond N. DuBois

Research output: Contribution to journalArticle

256 Citations (Scopus)

Abstract

Cyclooxygenase-derived prostaglandin E2 (PGE2) is the predominant prostanoid found in most colorectal cancers (CRC) and is known to promote colon carcinoma growth and invasion. However, the key downstream signaling pathways necessary for PGE2-induced intestinal carcinogenesis are unclear. Here we report that PGE2 indirectly transactivates PPARδ through PI3K/Akt signaling, which promotes cell survival and intestinal adenoma formation. We also found that PGE2 treatment of Apcmin mice dramatically increased intestinal adenoma burden, which was negated in Apcmin mice lacking PPARδ. We demonstrate that PPARδ is a focal point of crosstalk between the prostaglandin and Wnt signaling pathways which results in a shift from cell death to cell survival, leading to increased tumor growth.

Original languageEnglish (US)
Pages (from-to)285-295
Number of pages11
JournalCancer Cell
Volume6
Issue number3
DOIs
StatePublished - Sep 2004
Externally publishedYes

Fingerprint

Peroxisome Proliferator-Activated Receptors
Dinoprostone
Adenoma
Transcriptional Activation
Growth
Prostaglandins
Cell Survival
Wnt Signaling Pathway
Prostaglandin-Endoperoxide Synthases
Phosphatidylinositol 3-Kinases
Colorectal Neoplasms
Colon
Carcinogenesis
Cell Death
Carcinoma
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Prostaglandin E2 promotes colorectal adenoma growth via transactivation of the nuclear peroxisome proliferator-activated receptor δ. / Wang, Dingzhi; Wang, Haibin; Shi, Qiong; Katkuri, Sharada; Walhi, Walter; Desvergne, Beatrice; Das, Sanjoy K.; Dey, Sudhansu K.; DuBois, Raymond N.

In: Cancer Cell, Vol. 6, No. 3, 09.2004, p. 285-295.

Research output: Contribution to journalArticle

Wang, D, Wang, H, Shi, Q, Katkuri, S, Walhi, W, Desvergne, B, Das, SK, Dey, SK & DuBois, RN 2004, 'Prostaglandin E2 promotes colorectal adenoma growth via transactivation of the nuclear peroxisome proliferator-activated receptor δ', Cancer Cell, vol. 6, no. 3, pp. 285-295. https://doi.org/10.1016/j.ccr.2004.08.011
Wang, Dingzhi ; Wang, Haibin ; Shi, Qiong ; Katkuri, Sharada ; Walhi, Walter ; Desvergne, Beatrice ; Das, Sanjoy K. ; Dey, Sudhansu K. ; DuBois, Raymond N. / Prostaglandin E2 promotes colorectal adenoma growth via transactivation of the nuclear peroxisome proliferator-activated receptor δ. In: Cancer Cell. 2004 ; Vol. 6, No. 3. pp. 285-295.
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