Obesity-associated NLRC4 inflammasome activation drives breast cancer progression

Ryan Kolb; Liem Phan; Nicholas Borcherding; Yinghong Liu; Fang Yuan; Ann M Janowski; Qing Xie; Kathleen R Markan; Wei Li; Matthew J Potthoff; Enrique Fuentes-Mattei; Lesley G Ellies; C Michael Knudson; Mong-Hong Lee; Sai-Ching J Yeung; Suzanne L Cassel; Fayyaz S Sutterwala; Weizhou Zhang

doi:10.1038/ncomms13007

Back

Obesity-associated NLRC4 inflammasome activation drives breast cancer progression

Journal article

Open access

Peer reviewed

Obesity-associated NLRC4 inflammasome activation drives breast cancer progression

Ryan Kolb, Liem Phan, Nicholas Borcherding, Yinghong Liu, Fang Yuan, Ann M Janowski, Qing Xie, Kathleen R Markan, Wei Li, Matthew J Potthoff, …

Nature communications, Vol.7(1), pp.13007-13007

10/06/2016

DOI: 10.1038/ncomms13007

PMCID: PMC5059727

PMID: 27708283

Files and links (1)

url

https://doi.org/10.1038/ncomms13007View

Published (Version of record) Open Access

Abstract

Obesity is associated with an increased risk of developing breast cancer and is also associated with worse clinical prognosis. The mechanistic link between obesity and breast cancer progression remains unclear, and there has been no development of specific treatments to improve the outcome of obese cancer patients. Here we show that obesity-associated NLRC4 inflammasome activation/ interleukin (IL)-1 signalling promotes breast cancer progression. The tumour microenvironment in the context of obesity induces an increase in tumour-infiltrating myeloid cells with an activated NLRC4 inflammasome that in turn activates IL-1β, which drives disease progression through adipocyte-mediated vascular endothelial growth factor A (VEGFA) expression and angiogenesis. Further studies show that treatment of mice with metformin inhibits obesity-associated tumour progression associated with a marked decrease in angiogenesis. This report provides a causal mechanism by which obesity promotes breast cancer progression and lays out a foundation to block NLRC4 inflammasome activation or IL-1β signalling transduction that may be useful for the treatment of obese cancer patients.

Details

Title: Subtitle: Obesity-associated NLRC4 inflammasome activation drives breast cancer progression
Creators: Ryan Kolb - Center for Immunology and Immune Based Diseases, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA
Liem Phan - Department of Molecular and Cellular Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
Nicholas Borcherding - Medical Scientist Training Program, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA
Yinghong Liu - Department of Nephrology, The Second Xiangya Hospital, Research Institute of Nephrology, Central South University, Changsha, Hunan 410011, China
Fang Yuan - Department of Nephrology, The Second Xiangya Hospital, Research Institute of Nephrology, Central South University, Changsha, Hunan 410011, China
Ann M Janowski - Interdisciplinary Graduate Program in Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA
Qing Xie - Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA
Kathleen R Markan - Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA
Wei Li - Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA
Matthew J Potthoff - Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA
Enrique Fuentes-Mattei - Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA
Lesley G Ellies - Department of Pathology, University of California, San Diego, La Jolla, California 92093, USA
C Michael Knudson - Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA
Mong-Hong Lee - Cancer Biology Graduate Program, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
Sai-Ching J Yeung - Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
Suzanne L Cassel - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA
Fayyaz S Sutterwala - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA
Weizhou Zhang - Cancer Genes and Pathway Holden Comprehensive Cancer Center, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA
Resource Type: Journal article
Publication Details: Nature communications, Vol.7(1), pp.13007-13007
DOI: 10.1038/ncomms13007
PMID: 27708283
PMCID: PMC5059727
NLM abbreviation: Nat Commun
ISSN: 2041-1723
eISSN: 2041-1723
Publisher: England
Grant note: T32 AI007517 / NIAID NIH HHS T32 AI007260 / NIAID NIH HHS T32 GM007337 / NIGMS NIH HHS K99 CA158055 / NCI NIH HHS R56 AI118719 / NIAID NIH HHS P30 CA086862 / NCI NIH HHS R00 CA158055 / NCI NIH HHS L30 CA199587 / NCI NIH HHS R01 CA203834 / NCI NIH HHS L60 MD006355 / NIMHD NIH HHS K01 DK111758 / NIDDK NIH HHS T32 AI007485 / NIAID NIH HHS K22 CA118182 / NCI NIH HHS R01 AI104706 / NIAID NIH HHS R01 CA200673 / NCI NIH HHS
Language: English
Date published: 10/06/2016
Academic Unit: Dermatology; Microbiology and Immunology; Pathology; Iowa Neuroscience Institute; Radiation Oncology; Neuroscience and Pharmacology
Record Identifier: 9984040390202771

Metrics

16 Record Views

191 Times Cited - Web of Science