CD47/SIRPα pathways: Functional diversity and molecular mechanisms

Cellular communication is required for the normal function and maintenance of homeostasis. The extracellular communications are mediated by cell surface receptors, which transmit signals for various cell functions. Cell defense also relies on distinguishing between self and non-self. The integrins belong to the transmembrane receptors family and serve a crucial function in cell-extracellular adhesion and cell-cell signaling. The cell surface integrin-associated protein, or CD47, is an important integrin regulator and performs an array of functions. The CD47 interacts with the signal regulatory protein α (SIRPα) and regulates adhesion, apoptosis, phagocytosis, proliferation, metabolism, activation, hematopoietic stem cell migration, and malignancies. The CD47 expression is increased in tumor cells to escape immune response. The anti-CD47 antibodies have shown promising therapeutic strategies in various clinical trials in the treatment of hematologic and solid tumors. In the current review, we discussed multifunctional roles, molecular mechanisms, and therapeutic strategies of tumors by utilizing CD47/SIRPα interactions.