Abstract 322: Functional significance of tyrosine phosphorylation of galectin-3 in prostate cancer progression
Authors: Balan Vitaly , Nangia-Makker Pratima , Raz Avraham 
Published: August 2012

Galectin-3 is a carbohydrate binding chimeric lectin, which interacts with intracellular glycoproteins, cell surface molecules and extracellular matrix proteins based on its intra and extracellular distribution. Galectin-3 is one of the most studied galectins in the family and affects various biological phenomena such as cell growth, adhesion, angiogenesis, apoptosis, motility and metastasis. This protein is widely expressed in various tumor cells and its expression is correlated with tumorigenesis, tumor progression and metastasis. The functions of galectin-3 are dependent on its binding partners, its localization and can change as a result of post-translational modifications such as cleavage and phosphorylation. Recently, we demonstrated that gal-3 can be phosphorylated by c-Abl at Tyr 79, 107 and 118; Tyr107 is the major phosphorylation site. It was also shown that galectin-3 can be cleaved by prostate specific antigen, chymotrypsin-like serine protease, after Tyr 107 and this cleavage destroys galectin-3 multivalency while preserving its carbohydrate-binding activity. In solution, galectin-3 largely occurs as a monomer. It can also form homodimer by self-association through its CRDs in the absence of its binding ligands. However, in the presence of its carbohydrate binding ligands, galectin-3 can polymerize up to pentamers through its N-terminal domain. Oligomerization is a unique feature of secreted galectin-3, which allows its function by forming ordered galectin-glycan structures, also called lattices, on the cell surface or through direct engagement of specific cell surface glycoconjugates by traditional ligand-receptor interactions. We suggest that phosphorylation on Tyr 107 may block the cleavage of galectin-3 by PSA. Our experiments confirm this hypothesis and we suggest a model describing the role of galectin-3 in prostate cells with increased activity of c-Abl and Arg kinase. We demonstrate that PSA resistant intact galectin-3 may exert biological activities through ligand cross-linking to boost the tumorigenesis and progression of prostate cancer, while the protein cleaved after Tyr 107 cannot. The effect of cleaved galectin-3 on angiogenesis, chemotaxis and cell motility was significantly lower compare to full-length galectin-3. We posit that post-translational modifications of galectin-3 in the cells are but one component of a constellation of factors contributing to cancer disease prevalence and severity. In conclusion, the data show that galectin-3 phosphorylated on Tyr 107 can be associated with metastasis, cell growth, and tumorigenicity of prostate cancer cells and thus might used as a marker for prognosis of prostate cancer and a therapeutic target for the treatment of prostate cancer.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 322. doi:1538-7445.AM2012-322