CD147 Is a Novel Chemotherapy or Prevention Target in Melanoma.

Abstract

CD147, also named as BSG, was first identified from F9 embryonal carcinoma cells (Miyauchi etal., 1990) and the human BSG locus on chromosome 19p13.3 containing 10 exons (Belton etal., 2008; Kaname etal., 1993; Liao etal., 2011), which encodes four alternatively spliced transcripts:CD147/Bsg-1,2,3,4 (Kaname etal., 1993; Liao etal., 2011). Bsg-1 has three Ig-like domains (CD147/Bsg-1) (Hanna etal., 2003; Ochrietor etal., 2003), while CD147/Bsg-3,4 contains a single Ig-like domain (Belton etal., 2008; Liao etal., 2011). Evidence shows that CD147/Bsg-2 is the most abundant and best characterized splice product, which contains two Ig-like domains (Weidle etal., 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 etal., 2010; Yurchenko etal., 2005). There are three glycosylation sites at three conserved asparagine (Asn 44, 152, and 186) in the CD147 N-terminal domain (Fadool etal., 1993; Tang etal., 2004; Yu etal., 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 etal., 2014; Riethdorf etal., 2006; Tang etal., 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 etal., 2006; Jiang etal., 2014; Ni etal., 2014; Tang etal., 2004).