Sprouty in Tumors of the Nervous System

The Sprouty (SPRY) proteins are evolutionarily conserved modulators of growth factor-induced signaling pathways. The four different SPRY isoforms (SPRY1-4) are implicated in different types of cancer, acting as oncogenes or tumor suppressors depending on the SPRY isoform and the malignancy. Despite being tumor suppressors in many types of cancer, SPRY1 is an oncogene in rhabdomyosarcoma, SPRY2 in colorectal cancer, and SPRY4 in gastric cancer. In this review, we summarize the current literature about the functions of SPRY1-4 in glioblastoma (GB) and neuroblastoma (NB). To further delineate the effects of SPRY1-4 in the tumorigenesis of the nervous system, we analyzed the association of SPRY1-4 with the overall and event/progression-free survival of patients with pediatric and adult glioma, GB, and NB using public datasets. Together, there is evidence that SPRY1 and -2 are oncogenes in GB, whereas the role of SPRY3 and -4 in GB is not well defined. In NB, SPRY2 acts as a tumor suppressor, whereas the effects of SPRY1, -3, and -4 in NB have not been investigated so far, although the survival analysis revealed increased survival of NB patients with low SPRY3 levels in different datasets. Thus, this review demonstrates the requirement for further studies about the functions of the SPRY proteins in tumors of the nervous system to define their clinical relevance as potential therapeutic targets in the future.