Role of galectin-8 as a modulator of cell adhesion and cell growth

Abstract

Galectin-8 belongs to the family of tandem-repeat type galectins. It consists as several isoforms, each made of two domains of approximately 140 amino-acids, both having a carbohydrate recognition domain (CRD). These domains are joined by a 'link peptide' of variable length. The human galectin-8 gene covers 33 kbp of genomic DNA. It is localized on chromosome 1 (1q42.11) and contains 11 exons. The gene produces by alternative splicing 14 different transcripts, altogether encoding 6 proteins. Galectin-8, like other galectins, is a secreted protein. Upon secretion galectin-8 acts as a physiological modulator of cell adhesion. When immobilized, it functions as a matrix protein equipotent to fibronectin in promoting cell adhesion by ligation and clustering of a selective subset of cell surface integrin receptors. Complex formation between galectin-8 and integrins involves sugar-protein interactions and triggers integrin-mediated signaling cascades such as Tyr phosphorylation of FAK and paxillin. In contrast, when present in excess as a soluble ligand, galectin-8 (like fibronectin) forms a complex with integrins that negatively regulates cell adhesion. Such a mechanism allows local signals emitted by secreted galectin-8 to specify territories available for cell adhesion and migration. Due to its dual effects on the adhesive properties of cells and its association with fibronectin, galectin-8 might be considered as a novel type of a matricellular protein. Galectin-8 levels of expression positively correlate with certain human neoplasms, prostate cancer being the best example studied thus far. The overexpressed lectin might give these neoplasms some growth and metastasis related advantages due to its ability to modulate cell adhesion and cellular growth. Hence, galectin-8 may modulate cell-matrix interactions and regulate cellular functions in a variety of physiological and pathological conditions.

Redundant and Antagonistic Functions of Galectin-1, -3, and -8 in the Elicitation of T Cell Responses

“…4E). This is in agreement with the fact that Gal-8 contains two CRDs with different glycan specificities that enables it to promote cell adhesion by linking the extracellular matrix and the cell surface (22). The strikingly different cellular phenotypes induced by Gal-1-8-1 and Gal-8 suggest that they might involve distinct mechanisms of cellular activation to induce the proliferation of T cells.…”

Structural basis for recognition of autophagic receptor NDP52 by the sugar receptor galectin-8

“…Indeed, several galectins are recognized as potential targets for both anti-cancer and antiinflammatory drugs 24,[30][31][32][33] . As GAL8 is involved in many cellular processes, including cell adhesion, apoptosis, innate immunity and bacterial clearance 12,16,24,34 , it would be useful to develop a small compound to modulate the function of GAL8. Therefore, this NAD-bound GAL8 structure can be used as a template for the design of such a compound.…”

Galectin-8 binds to LFA-1, blocks its interaction with ICAM-1 and is counteracted by anti-Gal-8 autoantibodies isolated from lupus patients

“…However, these studies did not provide evidence of functional implications for this putative interaction. Tribulatti et al, (2009) studied Gal-8 bound proteins by mass spectrometry analysis in mice splenocytes and found several leukocyte surface glycoproteins, including previously reported integrins (Hadari et al, 2000;Zick et al, 2004;Cárcamo et al, 2006;Yamamoto et al, 2008) and CD45, as candidate counter-receptors. Their functional studies then focused on CD45, leaving LFA-1 unexplored (Tribulatti et al, 2009).…”