TSPAN33

Cluster of differentiation 53 (CD53) also known as OX44 or tetraspanin 25 (TSPAN25) is a glycoprotein belonging to the tetraspanin family. Members of the tetraspanin family are characterized by four transmembrane domains, including intracellular N- and C-termini, and small and large extracellular domains. Currently, the function of CD53 in teleost is not well understood. In this study, we identified a CD53 (named SmCD53) from turbot (Scophthalmus maximus) and examined its expression and biological activity. SmCD53 contained 231 amino acid residues and was predicted to be a tetraspanin with small and large extracellular domains. SmCD53 expression was observed in different tissues, particularly in immune-related organs. Experimental infection with bacterial or viral pathogen significantly up-regulated SmCD53 expression in a time-dependent manner. Immunofluorescence microscopy analysis showed that SmCD53 was localized on the surface of PBL and was recognized by antibody against its large extracellular domain. Ligation of SmCD53 onto PBLs with antibodies suppressed the respiratory burst activity, inflammatory reaction, and enhanced cell viability. SmCD53 knockdown significantly enhanced bacterial dissemination and proliferation in turbot. Overall, these results underscore the importance of CD53 in the maintenance of the function and homeostasis of the immune system.

B cell trafficking involves the coordinated activity of multiple adhesive and cytokine-receptor interactions, and the players in this process are not fully understood. In this study, we identified the tetraspanin CD53 as a critical regulator of both normal and malignant B cell trafficking. CXCL12 is a key chemokine in B cell homing to the bone marrow and secondary lymphoid organs, and both normal and malignant B cells from Cd53-/- mice have reduced migration toward CXCL12 in vitro, as well as impaired marrow homing in vivo. Using proximity ligation studies, we identified the CXCL12 receptor, CXCR4, as a novel, to our knowledge, CD53 binding partner. This interaction promotes receptor function, because Cd53-/- B cells display reduced signaling and internalization of CXCR4 in response to CXCL12. Together, our data suggest that CD53 interacts with CXCR4 on both normal and malignant B cells to promote CXCL12 signaling, receptor internalization, and marrow homing.

Tetraspanins (TSPANs) are a class of four-transmembrane segmented proteins. The precise functions of TSPANs and their roles in pan-cancer are unclear. In this work, we analyzed TSPAN1, TSPAN10, TSPAN11, TSPAN12, TSPAN13, TSPAN14, TSPAN15, TSPAN16, TSPAN17, TSPAN18, TSPAN18-AS1, TSPAN19, TSPAN2, TSPAN3, TSPAN31, TSPAN32, TSPAN33, TSPAN4, TSPAN5, TSPAN6, TSPAN7, TSPAN8, TSPAN9, TSPAN9-IT1 (24 TSPAN family genes) in relation to tumor characteristics from 11,057 TCGA samples across 33 cancer types. On 24 TSPAN family genes, multidimensional studies were conducted, including gene differential expression, immunological subtype analysis, clinical analysis, stemness indices analysis, drug sensitivity analysis, alteration analysis, and multi-omics validation (including ATAC-seq validation, single-cell sequencing validation, and other external validation). Genes were differentially expressed in 33 cancers, and several of them showed high consistency in terms of tumor characteristics. In particular, the potential roles of TSPAN15 and TSPAN1 in cancer deserve further attention.