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

doi:10.1016/j.ccr.2004.08.011

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 journal › Article › peer-review

301 Scopus citations

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 Apc^min mice dramatically increased intestinal adenoma burden, which was negated in Apc^min 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 language	English (US)
Pages (from-to)	285-295
Number of pages	11
Journal	Cancer cell
Volume	6
Issue number	3
DOIs	https://doi.org/10.1016/j.ccr.2004.08.011
State	Published - Sep 2004
Externally published	Yes

ASJC Scopus subject areas

Oncology
Cancer Research

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@article{7fc99ef5a94b4bd7902bbba2c5491b97,

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

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.",

author = "Dingzhi Wang and Haibin Wang and Qiong Shi and Sharada Katkuri and Walter Walhi and Beatrice Desvergne and Das, {Sanjoy K.} and Dey, {Sudhansu K.} and DuBois, {Raymond N.}",

note = "Funding Information: This work is supported in part from the United States Public Health Services Grants RO1DK 47279 (R.N.D.), P0-CA-77839 (R.N.D.), HD 33994, and DA06668 (S.K.D.). RND is the Hortense B. Ingram Professor of Molecular Oncology. R.N.D. (R37-DK47297) and S.K.D. (R37-HD12304) are recipients of NIH MERIT awards. We also thank the T.J. Martell Foundation and the National Colorectal Cancer Research Alliance (NCCRA) for generous support (R.N.D.). H.W. is a Lalor foundation fellow.",

year = "2004",

month = sep,

doi = "10.1016/j.ccr.2004.08.011",

language = "English (US)",

volume = "6",

pages = "285--295",

journal = "Cancer cell",

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publisher = "Cell Press",

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TY - JOUR

T1 - Prostaglandin E2 promotes colorectal adenoma growth via transactivation of the nuclear peroxisome proliferator-activated receptor δ

AU - Wang, Dingzhi

AU - Wang, Haibin

AU - Shi, Qiong

AU - Katkuri, Sharada

AU - Walhi, Walter

AU - Desvergne, Beatrice

AU - Das, Sanjoy K.

AU - Dey, Sudhansu K.

AU - DuBois, Raymond N.

N1 - Funding Information: This work is supported in part from the United States Public Health Services Grants RO1DK 47279 (R.N.D.), P0-CA-77839 (R.N.D.), HD 33994, and DA06668 (S.K.D.). RND is the Hortense B. Ingram Professor of Molecular Oncology. R.N.D. (R37-DK47297) and S.K.D. (R37-HD12304) are recipients of NIH MERIT awards. We also thank the T.J. Martell Foundation and the National Colorectal Cancer Research Alliance (NCCRA) for generous support (R.N.D.). H.W. is a Lalor foundation fellow.

PY - 2004/9

Y1 - 2004/9

N2 - 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.

AB - 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.

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JO - Cancer cell

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

Abstract

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