IL-6 promotes prostate tumorigenesis and progression through autocrine cross-activation of IGF-IR

As an established mediator of inflammation, IL-6 is implicated to facilitate prostate cancer progression to androgen independence through transactivation of the androgen receptor. However, whether IL-6 plays a causative role in de novo prostate tumorigenesis was never investigated. We now provide th...

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Main Authors:	Rojas, Andres, Liu, Gang, Coleman, Ilsa, Nelson, Peter S., Zhang, Miqin, Dash, Rupesh, Fisher, Paul B, Plymate, Stephen R., Wu, Jennifer D.
Format:	Online
Language:	English
Published:	2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3112005/

id	pubmed-3112005
recordtype	oai_dc
spelling	pubmed-31120052011-11-19 IL-6 promotes prostate tumorigenesis and progression through autocrine cross-activation of IGF-IR Rojas, Andres Liu, Gang Coleman, Ilsa Nelson, Peter S. Zhang, Miqin Dash, Rupesh Fisher, Paul B Plymate, Stephen R. Wu, Jennifer D. Article As an established mediator of inflammation, IL-6 is implicated to facilitate prostate cancer progression to androgen independence through transactivation of the androgen receptor. However, whether IL-6 plays a causative role in de novo prostate tumorigenesis was never investigated. We now provide the first evidence that IL-6 can induce tumorigenic conversion and further progression to an invasive phenotype of non-tumorigenic benign prostate epithelial cells. Moreover, we find that paracrine IL-6 stimulates autocrine IL-6 loop and autocrine activation of IGF-IR to confer the tumorigenic property and that activation of STAT3 is critical in these processes. Inhibition of STAT3 activation or IGF-IR signaling suppresses IL-6-mediated malignant conversion and the associated invasive phenotype. Inhibition of STAT3 activation suppresses IL-6-induced upregulation of IGF-IR and its ligands IGF-I and IGF-II. These findings indicate IL-6 signaling cooperates with IGF-IR signaling in the prostate microenvironment to promote prostate tumorigenesis and progression to aggressiveness. Our findings suggest that STAT3 and IGF-IR may represent potential effective targets for prevention or treatment of prostate cancer. 2011-01-24 2011-05-19 /pmc/articles/PMC3112005/ /pubmed/21258401 http://dx.doi.org/10.1038/onc.2010.605 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Rojas, Andres Liu, Gang Coleman, Ilsa Nelson, Peter S. Zhang, Miqin Dash, Rupesh Fisher, Paul B Plymate, Stephen R. Wu, Jennifer D.
spellingShingle	Rojas, Andres Liu, Gang Coleman, Ilsa Nelson, Peter S. Zhang, Miqin Dash, Rupesh Fisher, Paul B Plymate, Stephen R. Wu, Jennifer D. IL-6 promotes prostate tumorigenesis and progression through autocrine cross-activation of IGF-IR
author_facet	Rojas, Andres Liu, Gang Coleman, Ilsa Nelson, Peter S. Zhang, Miqin Dash, Rupesh Fisher, Paul B Plymate, Stephen R. Wu, Jennifer D.
author_sort	Rojas, Andres
title	IL-6 promotes prostate tumorigenesis and progression through autocrine cross-activation of IGF-IR
title_short	IL-6 promotes prostate tumorigenesis and progression through autocrine cross-activation of IGF-IR
title_full	IL-6 promotes prostate tumorigenesis and progression through autocrine cross-activation of IGF-IR
title_fullStr	IL-6 promotes prostate tumorigenesis and progression through autocrine cross-activation of IGF-IR
title_full_unstemmed	IL-6 promotes prostate tumorigenesis and progression through autocrine cross-activation of IGF-IR
title_sort	il-6 promotes prostate tumorigenesis and progression through autocrine cross-activation of igf-ir
description	As an established mediator of inflammation, IL-6 is implicated to facilitate prostate cancer progression to androgen independence through transactivation of the androgen receptor. However, whether IL-6 plays a causative role in de novo prostate tumorigenesis was never investigated. We now provide the first evidence that IL-6 can induce tumorigenic conversion and further progression to an invasive phenotype of non-tumorigenic benign prostate epithelial cells. Moreover, we find that paracrine IL-6 stimulates autocrine IL-6 loop and autocrine activation of IGF-IR to confer the tumorigenic property and that activation of STAT3 is critical in these processes. Inhibition of STAT3 activation or IGF-IR signaling suppresses IL-6-mediated malignant conversion and the associated invasive phenotype. Inhibition of STAT3 activation suppresses IL-6-induced upregulation of IGF-IR and its ligands IGF-I and IGF-II. These findings indicate IL-6 signaling cooperates with IGF-IR signaling in the prostate microenvironment to promote prostate tumorigenesis and progression to aggressiveness. Our findings suggest that STAT3 and IGF-IR may represent potential effective targets for prevention or treatment of prostate cancer.
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3112005/
_version_	1611458687854968832

IL-6 promotes prostate tumorigenesis and progression through autocrine cross-activation of IGF-IR

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