[Show abstract][Hide abstract] ABSTRACT: Galectins are a family of proteins involved in several cell processes, including their survival and death. Galectin-3 has in particular been described as an anti-apoptotic molecule entangled with a number of subcellular activities including anoikis resistance. In this work we partially address the mechanisms underlying this activity pointing at two key factors in injury progression: the alteration of mitochondrial membrane potential and the formation of reactive oxygen species. Overexpression of galectin-3 appears in fact to exert a protective effect towards both these events. On the basis of these data, we propose a reappraisal of the role of galectin-3 as a regulator of mitochondrial homeostasis.
[Show abstract][Hide abstract] ABSTRACT: Galectin-3 is a carbohydrate-binding protein endowed with affinity for beta-galactosides. It plays a role in cell-cell and cell-matrix interactions. Furthermore, it has been hypothesized to be involved in tumor progression and metastasis. To address the role of galectin-3 in the invasive and metastatic processes, we stably overexpressed galectin-3 in human breast carcinoma cell lines, and we evaluated the influence of elevated galectin-3 expression on several cell features, including cellular homotypic and heterotypic interactions and cell survival. No differences in various parameters related with cell growth features and proliferation were detected. By contrast, we found that galectin-3 overexpressing cells, with respect to low galectin-3 expressing cells, exerted: (1) a significantly enhanced adhesion to laminin, fibronectin and vitronectin exerted both directly or via increased expression of specific integrins, e.g., alpha-4 and beta-7; (2) a remodeling of those cytoskeletal elements associated with cell spreading, i.e., microfilaments; (3) an enhanced survival upon exposure to different apoptotic stimuli, such as cytokine and radiation. Collectively, our results indicate that overexpression of galectin-3 may play a role in tumor cell invasion and metastasis by specifically influencing cell adhesion to the extracellular matrix. This may confer selective survival advantage and resistance to the particular homeless-induced apoptosis called anoikia.
International Journal of Cancer 03/2000; 85(4):545-54. DOI:10.1002/(SICI)1097-0215(20000215)85:43.3.CO;2-E · 5.09 Impact Factor