Crosstalk between peroxisome proliferator-activated receptor δ and VEGF stimulates cancer progression

Dingzhi Wang, Haibin Wang, Yong Guo, Wei Ning, Sharada Katkuri, Walter Wahli, Beatrice Desvergne, Sudhansu K. Dey, Raymond N. DuBois

Research output: Contribution to journalArticle

132 Citations (Scopus)

Abstract

Peroxisome proliferator-activated receptor (PPAR) δ is a member of the nuclear hormone receptor superfamily. PPARδ may ameliorate metabolic diseases such as obesity and diabetes. However, PPARδ's role in colorectal carcinogenesis remains controversial. Here, we present genetic and pharmacologic evidence demonstrating that deletion of PPARδ decreases intestinal adenoma growth in ApcMin/+ mice and inhibits tumor-promoting effects of a PPARδ agonist GW501516. More importantly, we found that activation of PPARδ up-regulated VEGF in colon carcinoma cells. VEGF directly promotes colon tumor epithelial cell survival through activation of PI3K-Akt signaling. These results not only highlight concerns about the use of PPARδ agonists for treatment of metabolic disorders in patients who are at high risk for colorectal cancer, but also support the rationale for developing PPARδ antagonists for prevention and/or treatment of cancer.

Original languageEnglish (US)
Pages (from-to)19069-19074
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number50
DOIs
StatePublished - Dec 12 2006
Externally publishedYes

Fingerprint

Peroxisome Proliferator-Activated Receptors
Vascular Endothelial Growth Factor A
Neoplasms
Colon
Metabolic Diseases
Cytoplasmic and Nuclear Receptors
Phosphatidylinositol 3-Kinases
Adenoma
Colorectal Neoplasms
Cell Survival
Carcinogenesis
Obesity
Epithelial Cells
Carcinoma
Therapeutics
Growth

Keywords

  • Apoptosis
  • Colorectal cancer

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Crosstalk between peroxisome proliferator-activated receptor δ and VEGF stimulates cancer progression. / Wang, Dingzhi; Wang, Haibin; Guo, Yong; Ning, Wei; Katkuri, Sharada; Wahli, Walter; Desvergne, Beatrice; Dey, Sudhansu K.; DuBois, Raymond N.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 50, 12.12.2006, p. 19069-19074.

Research output: Contribution to journalArticle

Wang, Dingzhi ; Wang, Haibin ; Guo, Yong ; Ning, Wei ; Katkuri, Sharada ; Wahli, Walter ; Desvergne, Beatrice ; Dey, Sudhansu K. ; DuBois, Raymond N. / Crosstalk between peroxisome proliferator-activated receptor δ and VEGF stimulates cancer progression. In: Proceedings of the National Academy of Sciences of the United States of America. 2006 ; Vol. 103, No. 50. pp. 19069-19074.
@article{075d8e0985384188bfc3e783b188b67b,
title = "Crosstalk between peroxisome proliferator-activated receptor δ and VEGF stimulates cancer progression",
abstract = "Peroxisome proliferator-activated receptor (PPAR) δ is a member of the nuclear hormone receptor superfamily. PPARδ may ameliorate metabolic diseases such as obesity and diabetes. However, PPARδ's role in colorectal carcinogenesis remains controversial. Here, we present genetic and pharmacologic evidence demonstrating that deletion of PPARδ decreases intestinal adenoma growth in ApcMin/+ mice and inhibits tumor-promoting effects of a PPARδ agonist GW501516. More importantly, we found that activation of PPARδ up-regulated VEGF in colon carcinoma cells. VEGF directly promotes colon tumor epithelial cell survival through activation of PI3K-Akt signaling. These results not only highlight concerns about the use of PPARδ agonists for treatment of metabolic disorders in patients who are at high risk for colorectal cancer, but also support the rationale for developing PPARδ antagonists for prevention and/or treatment of cancer.",
keywords = "Apoptosis, Colorectal cancer",
author = "Dingzhi Wang and Haibin Wang and Yong Guo and Wei Ning and Sharada Katkuri and Walter Wahli and Beatrice Desvergne and Dey, {Sudhansu K.} and DuBois, {Raymond N.}",
year = "2006",
month = "12",
day = "12",
doi = "10.1073/pnas.0607948103",
language = "English (US)",
volume = "103",
pages = "19069--19074",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "50",

}

TY - JOUR

T1 - Crosstalk between peroxisome proliferator-activated receptor δ and VEGF stimulates cancer progression

AU - Wang, Dingzhi

AU - Wang, Haibin

AU - Guo, Yong

AU - Ning, Wei

AU - Katkuri, Sharada

AU - Wahli, Walter

AU - Desvergne, Beatrice

AU - Dey, Sudhansu K.

AU - DuBois, Raymond N.

PY - 2006/12/12

Y1 - 2006/12/12

N2 - Peroxisome proliferator-activated receptor (PPAR) δ is a member of the nuclear hormone receptor superfamily. PPARδ may ameliorate metabolic diseases such as obesity and diabetes. However, PPARδ's role in colorectal carcinogenesis remains controversial. Here, we present genetic and pharmacologic evidence demonstrating that deletion of PPARδ decreases intestinal adenoma growth in ApcMin/+ mice and inhibits tumor-promoting effects of a PPARδ agonist GW501516. More importantly, we found that activation of PPARδ up-regulated VEGF in colon carcinoma cells. VEGF directly promotes colon tumor epithelial cell survival through activation of PI3K-Akt signaling. These results not only highlight concerns about the use of PPARδ agonists for treatment of metabolic disorders in patients who are at high risk for colorectal cancer, but also support the rationale for developing PPARδ antagonists for prevention and/or treatment of cancer.

AB - Peroxisome proliferator-activated receptor (PPAR) δ is a member of the nuclear hormone receptor superfamily. PPARδ may ameliorate metabolic diseases such as obesity and diabetes. However, PPARδ's role in colorectal carcinogenesis remains controversial. Here, we present genetic and pharmacologic evidence demonstrating that deletion of PPARδ decreases intestinal adenoma growth in ApcMin/+ mice and inhibits tumor-promoting effects of a PPARδ agonist GW501516. More importantly, we found that activation of PPARδ up-regulated VEGF in colon carcinoma cells. VEGF directly promotes colon tumor epithelial cell survival through activation of PI3K-Akt signaling. These results not only highlight concerns about the use of PPARδ agonists for treatment of metabolic disorders in patients who are at high risk for colorectal cancer, but also support the rationale for developing PPARδ antagonists for prevention and/or treatment of cancer.

KW - Apoptosis

KW - Colorectal cancer

UR - http://www.scopus.com/inward/record.url?scp=34047243022&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34047243022&partnerID=8YFLogxK

U2 - 10.1073/pnas.0607948103

DO - 10.1073/pnas.0607948103

M3 - Article

VL - 103

SP - 19069

EP - 19074

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 50

ER -