Cluster of differentiation 151 (CD151) is a member of the mammalian tetraspanin family, which is involved in diverse functions such as maintaining normal cellular integrity, cell-to-cell communication, wound healing, platelet aggregation, trafficking, cell motility and angiogenesis. CD151 also supports de novo carcinogenesis in human skin squamous cell carcinoma (SCC) and tumor metastasis.
CD151 interacts with α3β1 and α6β4 integrins through palmitoylation where cysteine plays an important role in the association of CD151 with integrins and non-integrin proteins.
Invasion and metastasis of cancer cells were diminished by decreasing CD151 association with integrins. CD151 functions at various stages of cancer, including metastatic cascade and primary tumor growth, thus reinforcing the importance of CD151 as a target in oncology.
The present review highlights the role of CD151 in tumor metastasis and its importance in cancer therapy.
Keywords: CD151, integrins, metastasis, tetraspanin
Insight on CD151 (Cluster of Differentiation 151)
Tetraspanins are four-transmembrane-spanning proteins with short cytoplasmic N- and C-termini and one small and one large extracellular domain, namely (EC1 and EC2), with a unique cysteine motif in EC2 domain.1
They are highly expressed on cell surface and/or intracellular vesicle. Palmitoylation of intracellular and juxtamembrane cysteine of tetraspanins along with specific integrins contributes to tetraspanin complex formation.
This complex formation protects tetraspanins from lysosomal degradation and promotes increased cell–cell interaction.2
CD151 (glycoprotein-27 (GP-27)/Red blood cell antigen MER 2 (MER 2)/platelet-endothelial tetraspan antigen-3 (PETA-3)/Raph blood group antigen (RAPH)/Membrane Glycoprotein SFA-1 (SFA-1)./tetraspanin-24 (TSPAN-24)) is a plasma membrane protein that belongs to tetraspanin superfamily.
CD151 forms tetraspanin web with integrins such as α3β1, α6β1, α7β1, and α6β4;2 membrane receptors; intracellular signaling molecules such as phosphoinositide 4-kinase (PI4K) and protein kinase C (PKC);3,4 immunoglobulin super family proteins and other tetraspanins such as CD9, CD81 and CD63. These tetraspanin-enriched microdomains (TEMs) serve as molecular facilitator.5
CD151 contains a potential tyrosine-based sorting motif in the C-terminal domain. The YXXφ (tyrosine linked with hydrophobic amino acid) motif (where φ is a hydrophobic residue) is required for endocytosis and sorting of proteins from the trans-Golgi network (TGN) to lysosomes for degradation. A mutation in the CD151 YXXφ motif diminishes CD151 internalization and affects integrin-dependent cell migration.6,7
The major functions of CD151 are maintenance of epithelial cell integrity, wound healing, platelet aggregation, regulation of membrane fusion, trafficking, cell motility, angiogenesis and tumor metastasis.8
It is normally expressed in endothelial cells and platelets and frequently overexpressed in cancer cells where it is functionally associated with cancer progression and metastasis.9