C-type lectin family XIV members and angiogenesis

Abstract

The growth and metastasis of tumors is dependent on angiogenesis. C-type lectins are carbohydrate-binding proteins with a diverse range of functions. The C-type lectin family XIV members are transmembrane glycoproteins, and all four members of this family have been reported to regulate angiogenesis, although the detailed mechanism of action has yet to be completely elucidated. They interact with extracellular matrix proteins and mediate cell-cell adhesion by their lectin-like domain. The aim of the present study was to summarize the available information on the function and mechanism of C-type lectin family XIV in angiogenesis and discuss their potential as targets for cancer therapy.

Keywords: C-type lectin family XIV; CD93; CLEC14A; angiogenesis; endosialin; thrombomodulin.

Figure 1.

C-type lectin family XIV group. All the four members have a set of conserved domains such as the CTLD and different number of EGF like repeat domains. Some members also have a PDZ binding motif in the C-terminal cytoplasmic tail. Location of the domains in the full-length proteins with amino acid residues is given in numbers. SP, signal peptide; CTLD, C-type lectin-like domain; EGF, Epidermal growth factor-like domain; TM, Transmembrane domain; Cyto, Cytoplasmic domain; PDZ, PDZ binding motif.

Figure 2.

Mechanism of regulation of angiogenesis by the members of C-type lectin family XIV. (A) Interaction of CLEC14A with Hsp70-1A leads to ERK phosphorylation and angiogenesis. CLEC14A interaction with MMRN2 promotes angiogenesis by unknown mechanisms. (B) Interaction between TM and fibronectin promotes angiogenesis by FAK phosphorylation and increased MMP9 production. (C) CD93 interaction with MMRN2, fibronectin fibril and α5β1 integrin promotes angiogenesis by FAK phosphorylation. (D) The interaction of the cytoplasmic domain of CD93 with moesin leads to cytoskeletal reorganization. (E) Endosialin interaction with MMRN2, collagen I/IV and fibronectin promotes angiogenesis by unknown mechanisms. Endosialin may have a role in expression of MMP9 and PlGF. TM, thrombomodulin; FN, fibronectin; Col. I/IV, collagen I/IV; Cyto, cytoplasmic domain.