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Neuropilins (Nrp1 and Nrp2) are transmembrane proteins that act as co-receptors and increase responses to growth factors (GFs). Some of the major Nrp functions include angiogenesis, proliferation, metastasis and inhibition of immune responses. Preclinical studies have also shown that Nrps are potential targets for cancer drug therapy.
The Nrp structure has five domains that bind different ligands. The a1, a2, and b1 domains bind SEMA3. VEGF binds to the b1 and b2 domain, and CendR binds to b1 domain. The Nrps interact with GF receptors and their ligands to increase signal responses. TGF-?1 exerts anti-proliferative and immunosuppressive effects. Canonical TGF-?1 signaling lead to apoptosis and inhibition of proliferation. SEMA3, interacting with Nrps and plexins, can activate axonal guidance and inhibits numerous immune functions. GFs, VEGF, and non-canonical TGF-?1 signaling enhance cell survival, migration, proliferation, angiogenesis, epithelial-mesenchymal transition (EMT) and metastasis.
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