GDF-15: A Multifunctional Modulator and Potential Therapeutic Target in Cancer.

Various pathological processes are associated with the aberrant expression and function of cytokines, especially those belonging to the transforming growth factor-β (TGF-β) family. Nevertheless, the functions of members of the TGF-β family in cancer progression and therapy are still uncertain. Growth differentiation factor- 15, which exists in intracellular and extracellular forms, is classified as a divergent member of the TGF-β superfamily. It has been indicated that GDF-15 is also connected to the evolution of cancer both positively and negatively depending upon the cellular state and environment. Under normal physiological conditions, GDF-15 inhibits early tumour promotion. However, its abnormal expression in advanced cancers causes proliferation, invasion, metastasis, cancer stem cell formation, immune escape and a reduced response to therapy. As a clinical indicator, GDF-15 can be used as a tool for the diagnosis and therapy of an extensive scope of cancers. Although some basic functions of GDF-15 are noncontroversial, their mechanisms remain unclear and complicated at the molecular level. Therefore, GDF-15 needs to be further explored and reviewed.