Functional roles of GDF15 in modulating microenvironment to promote carcinogenesis.

Obesity and related metabolic dysregulation are risk factors for many types of cancer. The interactions between a developing tumor and its microenvironment are known to implicate a complex "crosstalk" among the factors produced by the population of cells. Among these factors, Growth and differentiation factor 15 (GDF15) has a functional role in cancer. GDF15 expression is induced in response to the conditions associated with cellular stress and diseases. The GDF15 receptor, a member of the glial-cell-derived neurotropic factor family (GDNF), is a GDNF family receptor α-like (GFRAL) protein. GDF15 induces pro-angiogenic effects in tumors. However, GDF15 could affect tumorigenesis both positively and negatively. With a better understanding of the upstream disease pathways reflected by GDF15, new treatment targets may emerge.