Targeting neuropilin-1 interactions is a promising anti-tumor strategy

Abstract

Neuropilins (NRP1 and NRP2) are multifunctional receptor proteins that are involved in nerve, blood vessel, and tumor development. NRP1 was first found to be expressed in neurons, but subsequent studies have demonstrated its surface expression in cells from the endothelium and lymph nodes. NRP1 has been demonstrated to be involved in the occurrence and development of a variety of cancers. NRP1 interacts with various cytokines, such as vascular endothelial growth factor family and its receptor and transforming growth factor β1 and its receptor, to affect tumor angiogenesis, tumor proliferation, and migration. In addition, NRP1 + regulatory T cells (Tregs) play an inhibitory role in tumor immunity. High numbers of NRP1 + Tregs were associated with cancer prognosis. Targeting NRP1 has shown promise, and antagonists against NRP1 have had therapeutic efficacy in preliminary clinical studies. NRP1 treatment modalities using nanomaterials, targeted drugs, oncolytic viruses, and radio-chemotherapy have gradually been developed. Hence, we reviewed the use of NRP1 in the context of tumorigenesis, progression, and treatment.

Solasonine Induces Apoptosis and Inhibits Proliferation of Bladder Cancer Cells by Suppressing NRP1 Expression

“…As single-pass transmembrane, non-tyrosine kinase surface glycoproteins, neuropilins (NRPs), are unique to vertebrates and highly conserved across species [ 50 ]. NRPs include two isoforms, NRP1 and NRP2.…”

“…The NRP1 protein consists of a long N-terminal extracellular domain, followed by a transmembrane region and a short cytosolic tail of 43–44 amino acids [ 22 ]. Its extracellular domain contains five subdomains, namely, a1, a2, b1, b2, and c, each of which mediates the interaction of NRP1 with different molecules and cells [ 50 ]. The b1 domain is the main functional domain responsible for NRP1 binding to the novel coronavirus disease 2019 receptors [ 53 , 54 ] and multiple growth factors and receptors, most notably VEGFA and VEGFR2 [ 60 ].…”

“…The NRP1-b1 domain is also a target for the design of many small-molecule agents. NRP1 binds to VEGFA and VEGFR2 simultaneously to form an NRP1/VEGFA/VEGFR2 complex, eliciting activation of downstream signal transduction pathways, including ERK/MAPK, P38/MAPK, and PI3K/AKT pathways [ 22 , 50 , 60 , 61 ]. Upstream regulator analysis by IPA identified both VEGF and EGFR as upstream regulators of solasonine-targeted genes.…”

Covid-19-Induced Dysautonomia: A Menace of Sympathetic Storm

“…Overexpression of NRP-1 in the CNS during SARS-CoV-2 infection contributes to the inhibition of anti-inflammatory Fas ligand with subsequent neuroinflammation and ANS dysfunction (Singh et al, 2021). Taken together, targeting of NRP-1 may reduce SARS-CoV-2 infectivity and neurological disorders in in particular DSN in COVID-19 (Liu et al, 2021).…”

The Role of Neuropilin-2 in the Epithelial to Mesenchymal Transition of Colorectal Cancer: A Systematic Review

“…Either NRP-1 or NRP-2 or both are expressed in nearly all tumor cells. Tumor development, progression, and therapy options have all been examined for NRP-1 [ 30 ]. Solid tumor development is aided when NRP-1 binds VEGF-A, while SEMA3A binding often improves prognosis by limiting tumor cell motility and invasion.…”