Genetic status of KRAS influences Transforming Growth Factor-beta (TGF-β) signaling: An insight into Neuropilin-1 (NRP1) mediated tumorigenesis

Oncogenic RAS and deregulated transforming growth factor-beta (TGF)-beta signaling have been implicated in several cancers. So far, attempts to target either one of them therapeutically have been futile as both of them are involved in multiple fundamental cellular processes and the normal forms are expressed by almost all cells. Hence, their inhibition would disrupt several physiological processes. Besides, their downregulation stimulates the tumor cells to develop adaptive mechanisms and would most likely be ineffective as therapeutic targets. Furthermore, growing literature suggests that both of these signaling pathways converge to enhance tumor development. Therefore, a lot of interest has been generated to explore the areas where these pathways interface that might identify new molecules that could potentially serve as novel therapeutic targets. In this review, we focus on such convergent signaling and cross-interaction that is mediated by neuropilin-1 (NRP1), a receptor that can interact with multiple growth factors including TGF-beta for promoting tumorigenesis process.