Journal article
Circulating Adipose Fatty Acid Binding Protein Is a New Link Underlying Obesity-Associated Breast/Mammary Tumor Development
Cell metabolism, Vol.28(5), pp.689-705.e5
11/06/2018
DOI: 10.1016/j.cmet.2018.07.006
PMCID: PMC6221972
PMID: 30100196
Abstract
It is clear that obesity increases the risk of many types of cancer, including breast cancer. However, the underlying molecular mechanisms by which obesity is linked to cancer risk remain to be defined. Herein, we report that circulating adipose fatty acid binding protein (A-FABP) promotes obesity-associated breast cancer development. Using clinical samples, we demonstrated that circulating A-FABP levels were significantly increased in obese patients with breast cancer in comparison with those without breast cancer. Circulating A-FABP released by adipose tissue directly targeted mammary tumor cells, enhancing tumor stemness and aggressiveness through activation of the IL-6/STAT3/ALDH1 pathway. Importantly, genetic deletion of A-FABP successfully reduced tumor ALHD1 activation and obesity-associated mammary tumor growth and development in different mouse models. Collectively, these data suggest circulating A-FABP as a new link between obesity and breast cancer risk, thereby revealing A-FABP as a potential new therapeutic target for treatment of obesity-associated cancers.
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•Circulating levels of A-FABP are elevated in obesity-associated breast cancer•Soluble A-FABP promotes mammary tumor stemness and aggressiveness•A-FABP-induced ALDH1 activity is dependent on IL-6/STAT3 signaling•A-FABP deficiency uncouples HFD-induced obesity and mammary tumor development
The links between obesity and cancer are not well understood. Hao et al. show that circulating adipose fatty acid binding protein (A-FABP) increases in obesity and promotes breast cancer by increasing mammary tumor stemness and aggressiveness through an IL-6/STAT3/ALDH1 axis. A-FABP could be a potential therapeutic target for obesity-associated cancers.
Details
- Title: Subtitle
- Circulating Adipose Fatty Acid Binding Protein Is a New Link Underlying Obesity-Associated Breast/Mammary Tumor Development
- Creators
- Jiaqing Hao - University of LouisvilleYuwen Zhang - University of LouisvilleXiaofang Yan - University of LouisvilleFei Yan - University of MinnesotaYanwen Sun - University of LouisvilleJun Zeng - University of LouisvilleSabine Waigel - University of LouisvilleYanhui Yin - Peking UniversityMostafa M. Fraig - University of LouisvilleNejat K. Egilmez - University of LouisvilleJill Suttles - University of LouisvilleMaiying Kong - University of LouisvilleShujun Liu - University of MinnesotaMargot P. Cleary - University of MinnesotaEdward Sauter - Hartford HospitalBing Li - University of Louisville
- Resource Type
- Journal article
- Publication Details
- Cell metabolism, Vol.28(5), pp.689-705.e5
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.cmet.2018.07.006
- PMID
- 30100196
- PMCID
- PMC6221972
- ISSN
- 1550-4131
- eISSN
- 1932-7420
- Language
- English
- Date published
- 11/06/2018
- Academic Unit
- Pathology; Surgery
- Record Identifier
- 9984696547002771
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