Semaphorin-4F (SEMA4F)

Semaphorin-4F (SEMA4F) is a transmembrane protein of the class IV semaphorin family that functions as a probable cell surface receptor involved in neural development, particularly guiding axon pathfinding and regulating migration and differentiation of oligodendroglial precursor cells[1][5]. SEMA4F plays key roles in heterotypic cell-cell contacts and signal transduction, mediating effects such as growth cone collapse in retinal ganglion cell axons and modulating neurogenesis in both normal physiology and cancer[2][3]. In cancer biology, SEMA4F is overexpressed in prostate and breast cancer, where it promotes cancer cell proliferation, migration, and perineural invasion, contributing to aggressive disease phenotypes. In prostate cancer, cytoplasmic SEMA4F expression correlates with poor prognosis and increased nerve density in tumors, suggesting its utility as a prognostic biomarker and emerging therapeutic target[2]. The protein contains a sema domain, immunoglobulin-like domain, and transmembrane domain, and may signal in autocrine/paracrine fashions in both nervous system and tumor microenvironments[1][2][4]. No approved drugs currently directly target SEMA4F, but it is considered a promising target for novel anti-cancer therapies focused on disrupting tumor–nerve interactions[2].

Other names

Semaphorin 4FSEMA4FSEMAMSEMAWSema MSema WSemaphorin-MSemaphorin-Wm-Sema MM-SEMAPRO2353S4Fsemaphorin-4FSsemaphorin 4FSema domain immunoglobulin domain transmembrane domain (TM) and short cytoplasmic domain (semaphorin) 4F

Potential antineoplastic mechanism via inhibition of SEMA4F-mediated axonogenesis, cancer proliferation/migration, or perineural invasion[2]