Regulation and biological functions of the CX3CL1-CX3CR1 axis and its relevance in solid cancer: A mini-review

Abstract

CX3CL1 is a transmembrane protein from which a soluble form can be generated by proteolytic shedding. Membranal and soluble forms of CX3CL1 exhibit different functions, although both bind to the CX3CR1 chemokine receptor. The CX3CL1-CX3CR1 axis mediates the adhesion of leukocytes and is also involved in cell survival and recruitment of immune cell subpopulations. The function of CX3CL1 is finely tuned by cytokines and transcription factors regulating its expression and post-translational modifications. On homeostasis, the CX3CL1-CX3CR1 axis participates in the removal of damaged neurons and neurogenesis, and it is also involved on several pathological contexts. The CX3CL1-CX3CR1 axis induces several cellular responses relevant to cancer such as proliferation, migration, invasion and apoptosis resistance. In this review, we address biological aspects of this molecular axis with important therapeutic potential, emphasizing its role in cancer, one of the most prevalent chronic diseases which significantly affect the quality of life and life expectancy of patients.