Pathogenic implication of the CD53 tetraspanin in immune and cancer cells

Tetraspanin proteins are a specific family of membrane proteins with four transmembrane domains forming a core that assembles different types of complexes by their interactions among themselves, and with other membrane, extracellular and intracellular proteins. These tetraspanin complexes modulate multiple signaling pathways and generate exosomes. Tetraspanin proteins have a heterogeneous distribution, some are expressed in many different cell types, while others are highly restricted to specific cell types. Among the latter is CD53 (TSPAN25), a tetraspanin protein that is mainly expressed in nucleated hematopoietic cells, although it has also been detected in some carcinomas. CD53 forms oligomeric complexes with other members of this protein family in cell membranes, which can assemble and release exosomes and intracellular vesicles. CD53 on the plasma membrane modulates cell adhesion, migration, cell proliferation and survival. CD53 has no known specific ligand, but its ligation with specific antibodies modulates different intracellular signals, among which is protecting cells from apoptosis that is mediated by phosphorylation and activation of Akt, increased Bcl-xL level, decreased Bax level, and reducing caspase activation. CD53 ligation also induces calcium mobilization, activation of PKC and DREAM complex, and expression of the inducible nitric oxide synthase gene resulting in increased nitric oxide production. The different biological roles of CD53 are implicated in the regulation of specific functions associated with both immune responses and tumor biology. However, the heterogeneity of the cell types and of the pathways in which CD53 participates need to be studied in combination with other tetraspanins in order to detect their cooperation and contribution in specific cell types, normal or tumoral.