Prostaglandin E(2) promotes colorectal adenoma growth via transactivation of the nuclear peroxisome proliferator-activated receptor delta

Cancer Cell
D WangR N Dubois

Abstract

Cyclooxygenase-derived prostaglandin E(2) (PGE(2)) 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 PGE(2)-induced intestinal carcinogenesis are unclear. Here we report that PGE(2) indirectly transactivates PPARdelta through PI3K/Akt signaling, which promotes cell survival and intestinal adenoma formation. We also found that PGE(2) treatment of Apc(min) mice dramatically increased intestinal adenoma burden, which was negated in Apc(min) mice lacking PPARdelta. We demonstrate that PPARdelta 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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Citations

Oct 19, 2011·Cancer Metastasis Reviews·Ashleigh E MooreDan A Dixon
Jan 7, 2011·Cancer Microenvironment : Official Journal of the International Cancer Microenvironment Society·Vijay G PeddareddigariRaymond N Dubois
Jun 2, 2010·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Vivek VaishSankar Nath Sanyal
Jan 28, 2009·Nature Chemical Biology·Jing-Ruey J YehRandall T Peterson
Nov 3, 2005·Nature Clinical Practice. Oncology·Jason R MannRaymond N DuBois
Apr 2, 2013·Nature Medicine·Carina ScholtysekGerhard Krönke
Feb 20, 2010·Nature Reviews. Cancer·Dingzhi Wang, Raymond N Dubois
Dec 2, 2006·Nature Reviews. Drug Discovery·Nick Barker, Hans Clevers
Nov 16, 2004·The Journal of Biological Chemistry·Michael G BacklundRaymond N DuBois
Mar 29, 2006·The Journal of Experimental Medicine·Dingzhi WangRaymond N DuBois
Jul 4, 2012·Antioxidants & Redox Signaling·Samar BasuMarie-Paule Vasson
Apr 27, 2007·Pharmacogenetics and Genomics·Jeannette BiglerCornelia M Ulrich
Feb 3, 2007·Current Opinion in Gastroenterology·William F Stenson
Nov 26, 2013·The Cancer Journal·Dingzhi Wang, Raymond N DuBois
Sep 20, 2006·Molecular and Cellular Biology·Pei-Chin ChuangShaw-Jenq Tsai
Aug 25, 2005·Gut·D Wang, R N Dubois
Nov 15, 2006·Annual Review of Medicine·Yong I Cha, Raymond N DuBois
Jul 18, 2009·American Journal of Physiology. Gastrointestinal and Liver Physiology·Akira MiyakiAndrew J Dannenberg
Jun 28, 2008·PPAR Research·Keisuke TachibanaTakefumi Doi
Aug 5, 2008·Cancer Research·Dingzhi WangRaymond N DuBois
Jan 21, 2010·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Elizabeth M PooleCornelia M Ulrich
Jan 14, 2009·Cancer Prevention Research·Sanford D Markowitz
Dec 15, 2011·Cancer Prevention Research·Martha J ShrubsoleWei Zheng
Jun 21, 2008·American Journal of Respiratory Cell and Molecular Biology·Tetyana V PedchenkoPierre P Massion
Jan 26, 2008·The Journal of Clinical Investigation·Boryana K PopivanovaNaofumi Mukaida
Apr 29, 2011·BMC Cancer·Lisenn LalierChristophe Olivier

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