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. 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.
Bibliographical noteFunding Information:
We thank Dr. Hyeran Jang from Research Diets for assistance with the design of custom rodent diets. We thank Dr. Adrienne Jordan for advice and interpretation of histopathology. This work was supported by NIH R01CA18098601A1 and NIH R01CA17767901A1 . Microarray assay was performed and analyzed by the Genomics Facility at the University of Louisville, which is supported by NIH P20GM103436 , NIH P30GM106396 , and the J.G. Brown Foundation .
© 2018 Elsevier Inc.
Copyright 2019 Elsevier B.V., All rights reserved.
- breast cancer development
- tumor stemness
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't
- Research Support, N.I.H., Extramural