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Abstract The incidence of breast cancer continues to rise each year despite significant advances in diagnosis and treatment. Obesity-associated dysregulated lipid metabolism is believed to contribute to the increasing risk of breast cancer. However, the mechanisms linking lipid dysregulation to breast cancer risk and progression remain to be determined. The family of fatty acid binding proteins (FABPs) evolves to facilitate lipid transport and metabolism. As the predominant isoforms of FABP members expressed in breast tissue, adipose FABP (A-FABP, also known as FABP4) and epithelial FABP (E-FABP, FABP5) have been shown to play critical roles in breast carcinogenesis. In this study, we collected surgical breast tissue samples from 96 women with different subtypes of breast cancer and comprehensively analyzed the expression pattens of FABP4 and FABP5. We found that distinct expression profiles of FABP4 and FABP5 were associated with their unique roles in breast cancer development. FABP4, mainly expressed in breast stroma, especially in adipose tissue, supported neighboring tumor cell lymphvascular invasion through secretion from adipocytes. In contrast, FABP5, primarily expressed in epithelial-derived tumor cells, promoted tumor metastasis by enhancing lipid metabolism. Thus, elevated levels of FABP4 and FABP5 could serve as poor prognostic markers for breast cancer. Inhibiting the activity of FABP4 and/or FABP5 may offer a novel strategy for breast cancer treatment.
Jiang et al. (Wed,) studied this question.