Semaphorin 3C (SEMA3C)

Semaphorin 3C (SEMA3C) is a **secreted glycoprotein ligand** of the Class 3 semaphorin family, widely conserved in vertebrates and characterized by a sema domain, immunoglobulin (Ig)-like domain, and basic domain[1][2][5][6]. It functions primarily as an **axon guidance cue and vascular guidance molecule**, signaling via receptor complexes containing neuropilin-1 or neuropilin-2 and plexins (notably Plexin-D1 and Plexin-B1)[1][2][7]. SEMA3C is **essential for proper neuronal and cardiovascular development**, acting as both a chemorepellent and chemoattractant depending on the context, and is crucial for processes such as axonal pathfinding and cardiac outflow tract formation[1][5][6]. Beyond development, SEMA3C is upregulated in several cancers and **drives oncogenic processes** including cell proliferation, migration, invasion, epithelial-to-mesenchymal transition, and resistance to hormonal therapy in prostate cancer[2][3]. It can transactivate receptor tyrosine kinases (EGFR, HER2, MET) and is transcriptionally regulated by the androgen receptor, especially in prostate cancer[2][3]. Inhibiting SEMA3C is a **therapeutic strategy under preclinical investigation** using small molecules, antibody biologics, and RNA-based modalities, but further development must contend with complex context-dependent functions and the risk of developmental toxicity[2][3].

Other names

Semaphorin-3CSEMAESema ESemESemaphorin-Esema domainimmunoglobulin domain (Ig)short basic domainsecreted semaphorin 3Csemaphorin Esema ESEMA3C isoform2

Disruption of SEMA3C binding to neuropilin-1 or neuropilin-2 coreceptors to inhibit downstream signaling[3] Blockade of SEMA3C-mediated activation of plexin family receptors and transactivation of multiple receptor tyrosine kinases (including EGFR, HER2, and MET)[2][3] Inhibition of SEMA3C-driven autocrine andromedin signaling in prostate cancer[2][3]