Overview of the molecular mechanisms contributing to the formation of cancer-associated adipocytes

Adipocytes are the main stromal cells in the tumor microenvironment. In addition to serving as energy stores for triglycerides, adipocytes may function as an active endocrine organ. The crosstalk between adipocytes and cancer cells was shown to promote the migration, invasion and proliferation of cancer cells and to cause phenotypic and functional changes in adipocytes. Tumor-derived soluble factors, such as TNF-α, plasminogen activator inhibitor 1, Wnt3a, IL-6, and exosomal microRNAs (miRNA/miRs), including miR-144, miR-126, miR-155, as well as other miRNAs, have been shown to act on adipocytes at the tumor invasion front, resulting in the formation of cancer-associated adipocytes (CAAs) with diminished reduced terminal differentiation markers and a dedifferentiated phenotype. In addition, the number and size of CAA lipid droplets have been found to be significantly reduced compared with those of mature adipocytes, whereas inflammatory cytokines and proteases are overexpressed. The aim of the present review was to summarize the latest findings on the biological changes of CAAs and the potential role of tumor-adipocyte crosstalk in the formation of CAAs, in the hope of providing novel perspectives for breast cancer treatment.