The emerging role of substance P/neurokinin-1 receptor signaling pathways in growth and development of tumor cells

Tachykinins (TKs) include an evolutionarily conserved group of small bio-active peptides which possess a common carboxyl-terminal sequence, Phe-X-Gly-Leu-Met-NH2. TKs also have been shown to have implications in different steps of carcinogenesis, such as angiogenesis, mitogenesis, metastasis, and other growth-related events. The biological actions of substance P (SP), as the most important member of the TK family, are mainly mediated through a G protein-coupled receptor named neurokinin-1 receptor (NK1R). More recently, it has become clear that SP/NK1R system is involved in the initiation and activation of signaling pathways involved in cancer development and progression. Therefore, SP may contribute to triggering a variety of effector mechanisms including protein synthesis and a number of transcription factors that modulate the expression of genes involved in these processes. The overwhelming insights into the blockage of NK1R using specific antagonists could suggest a therapeutic approach in cancer therapy. In this review, we focus on evidence supporting an association between the signaling pathways of the SP/NK1R system and cancer cell proliferation and development.