Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/146661
Title: Obesity-associated inflammation promotes angiogenesis and breast cancer via angiopoietin-like 4
Authors: Kolb, Ryan
Kluz, Paige
Tan, Zhen Wei
Borcherding, Nicholas
Bormann, Nicholas
Vishwakarma, Ajaykumar
Balcziak, Louis
Zhu, Pengcheng
Davies, Brandon S. J.
Gourronc, Francoise
Liu, Ling-Zhi
Ge, Xin
Jiang, Bing-Hua
Gibson-Corley, Katherine
Klingelhutz, Aloysius
Tan, Nguan Soon
Zhu, Yuwen
Sutterwala, Fayyaz S.
Shen, Xian
Zhang, Weizhou
Keywords: Science::Medicine
Issue Date: 2018
Source: Kolb, R., Kluz, P., Tan, Z. W., Borcherding, N., Bormann, N., Vishwakarma, A., . . . Zhang, W. (2019). Obesity-associated inflammation promotes angiogenesis and breast cancer via angiopoietin-like 4. Oncogene, 38(13), 2351-2363. doi:10.1038/s41388-018-0592-6
Project: MOE2014-T2-1-012
Journal: Oncogene
Abstract: Obesity is a risk factor for breast cancer and also predicts poor clinical outcomes regardless of menopausal status. Contributing to the poor clinical outcomes is the suboptimal efficacy of standard therapies due to dose limiting toxicities and obesity-related complications, highlighting the need to develop novel therapeutic approaches for treating obese patients. We recently found that obesity leads to an increase in tumor-infiltrating macrophages with activated NLRC4 inflammasome and increased interleukin (IL)−1β production. IL-1β, in turn, leads to increased angiogenesis and cancer progression. Using Next Generation RNA sequencing, we identified an NLRC4/IL-1β-dependent upregulation of angiopoietin-like 4 (ANGPTL4), a known angiogenic factor in cancer, in tumors from obese mice. ANGPTL4-deficiency by genetic knockout or treatment with a neutralizing antibody led to a significant reduction in obesity-induced angiogenesis and tumor growth. At a mechanistic level, ANGPTL4 expression is induced by IL-1β from primary adipocytes in a manner dependent on NF-κB- and MAP kinase-activation, which is further enhanced by hypoxia. This report shows that adipocyte-derived ANGPTL4 drives disease progression under obese conditions and is a potential therapeutic target for treating obese breast cancer patients.
URI: https://hdl.handle.net/10356/146661
ISSN: 0950-9232
DOI: 10.1038/s41388-018-0592-6
Rights: © 2018 Springer Nature Limited. All rights reserved. This paper was published in Oncogene and is made available with permission of Springer Nature Limited.
Fulltext Permission: open
Fulltext Availability: With Fulltext
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