How Are Breast Cancer and Obesity Related? Possible New Link Discovered

There is a greater risk of hormone receptor—positive breast cancer if a patient is obese. Researchers from the University of Louisville James Graham Brown Cancer Center have discovered a possible new link between obesity and a greater risk for developing breast cancer: adipose fatty acid binding protein, or FABP4. Their results published online last week in Trends in Molecular Medicine demonstrate a likely connection between accumulation of fat tissue, the release of greater amounts of circulating FABP4, and breast cancer tumor growth.

“In our research, we found the fatty acid binding protein family, especially one member, FABP4, plays a very critical role in the association of obesity and cancer, most specifically breast cancer. We theorize that FABP4 is responsible for the underlying molecular mechanism which promotes obesity-associated breast cancer development,” stated Bing Li, PhD, associate professor in the department of microbiology and immunology and James Graham Brown Cancer Center at the University of Louisville, and one of the study’s authors.

He proposes 2 mechanisms of action for why the connection exists:

1. There are higher levels of FABP4 in certain tumor-associated macrophages, which promote tumor growth.
2. The more fat, or adipose, tissue we have, the more FABP4 is released into circulation, which leads to more communication with breast cancer cells and the promotion of breast cancer development.

“When we get obese, this protein is secreted out much more into the circulatory system,” Li said. “Normally these molecules are inside the cells, but when people are obese, the molecules are outside.”

The FABP4 family of proteins evolved as a way for water-soluble dietary long-chain fatty acids to be absorbed and used by our tissues. Essentially, they are the logistic engineers for where fatty acids go and how they are used. However, individuals who are considered obese have greater amounts of adipose tissue, which is an indicator of higher levels of FABP4, and that increases their body mass index and affects hormone production.

Additional evidence shows that FABP4 “is able to bind [free fatty acids] and provide energy for rapid ovarian tumor growth and metastasis,” as well as blocks the activity of tumor-suppressor genes in myeloid-derived leukemia cells. Therefore, the study results indicate, hindering FABP4 could hinder tumor growth.

“Targeting FABP4 with either small molecular inhibitors or specific antibodies has been shown to be feasible in other disease settings. Considering the persistent risk of breast cancer recurrence after current therapeutic strategies,” the study authors noted, “inhibition of FABP4 activity might offer a novel strategy for the treatment of obesity-associated breast cancer.”

Reference

Zeng J, Sauter ER, Li B. FABP4: a new player in obesity-associated breast cancer [published online April 7, 2020]. Trends Mol Med. doi: 10.1016/j.molmed.2020.03.004