CD147 Is a Novel Chemotherapy or Prevention Target in Melanoma.

CD147, also named as BSG, was first identified from F9 embryonal carcinoma cells (Miyauchi et al., 1990) and the human BSG locus on chromosome 19p13.3 containing 10 exons (Belton et al., 2008; Kaname et al., 1993; Liao et al., 2011), which encodes four alternatively spliced transcripts:CD147/Bsg-1,2,3,4 (Kaname et al., 1993; Liao et al., 2011). Bsg-1 has three Ig-like domains (CD147/Bsg-1) (Hanna et al., 2003; Ochrietor et al., 2003), while CD147/Bsg-3,4 contains a single Ig-like domain (Belton et al., 2008; Liao et al., 2011). Evidence shows that CD147/Bsg-2 is the most abundant and best characterized splice product, which contains two Ig-like domains (Weidle et al., 2010). Analysis of amino acids showed that CD147 contains a single-chain type I transmembrane domain composed of a 21-amino acid signal sequence, an extracellular domain consisting of 186 amino acids with two Ig-like domains and a cytoplasmic domain of 41 residues (Kanekura et al., 2010; Yurchenko et al., 2005). There are three glycosylation sites at three conserved asparagine (Asn 44, 152, and 186) in the CD147 N-terminal domain (Fadool et al., 1993; Tang et al., 2004; Yu et al., 2006), which could explain the molecular mass of CD147 shifts from a predicted molecular weight of about 27 kDa to 40-65 kDa with Western blotting. Inhibition of glycosylation by specific inhibitors showed that on carbohydrate side groups bearing β-1,6-branched, polylactosamine-type sugars, fucosylations are the major glycosylation type in N-glycosylation of CD147 (Ni et al., 2014; Riethdorf et al., 2006; Tang et al., 2004). In addition, N-glycosylation of CD147 has been identified as low glycosylated (approximately 32 kDa) or high glycosylated (approximately 45-65 kDa). The fully glycosylated mature CD147 (high-glycosylated CD147) is translocated to the plasma membrane, while low-glycosylated CD147 is the precursor of high-glycosylated CD147 in the endoplasmic reticulum, which requires additional modification in the Golgi prior to being expressed on the cell surface; high levels of glycosylation are a primary biochemical property of CD147 (Jia et al., 2006; Jiang et al., 2014; Ni et al., 2014; Tang et al., 2004).