Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17931 (galectin-3)
 2,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Galectin-3 is a member of a growing family of animal beta-galactoside-binding proteins shown to be involved in cell growth, differentiation, apoptosis resistance, and tumor progression. In the present study, we investigated whether galectin-3 can protect against apoptosis induced by the loss of cell anchorage (anoikis). Because studies suggest that cellular sensitivity to anoikis is associated with cell cycle regulation, we examined the role of galectin-3 on cell cycle regulation. Although BT549 cells (human breast epithelial cells) undergo anoikis, galectin-3-overexpressing BT549 cells respond to the loss of cell adhesion by inducing G1 arrest without detectable cell death. Galectin-3-mediated G1 arrest involves down-regulation of G1-S cyclin levels (cyclin E and cyclin A) and up-regulation of their inhibitory protein levels (p21(WAF1/CIP1) and p27KIP1). After the loss of cell anchorage, Rb protein becomes hypophosphorylated in galectin-3-overexpressing cells, as predicted from the flow cytometric analysis and immunoblot analysis of cyclins and their inhibitors. Interestingly, galectin-3 induces cyclin D1 expression (an early G1 cyclin) and its associated kinase activity in the absence of cell anchorage. On the basis of these results, we propose that galectin-3 inhibition of anoikis involves cell cycle arrest at an anoikis-insensitive point (late G1) through modulation of gene expression and activities of cell cycle regulators. The present study suggests that galectin-3 may be a critical determinant for anchorage-independent cell survival of disseminating cancer cells in the circulation during metastasis.
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PMID:Cell cycle arrest and inhibition of anoikis by galectin-3 in human breast epithelial cells. 1046 21

Galectin-3, a beta-galactoside-binding protein, is implicated in cell growth, adhesion, differentiation, and tumor progression by interactions with its ligands. Recent studies have revealed that galectin-3 suppresses apoptosis and anoikis that contribute to cell survival during metastatic cascades. Previously, it has been shown that human galectin-3 undergoes post-translational signaling modification of Ser(6) phosphorylation that acts as an "on/off" switch for its sugar-binding capability. We questioned whether galectin-3 phosphorylation is required for its anti-apoptotic function. Serine to alanine (S6A) and serine to glutamic acid (S6E) mutations were produced at the casein kinase I phosphorylation site in galectin-3. The cDNAs were transfected into a breast carcinoma cell line BT-549 that innately expresses no galectin-3. Metabolic labeling revealed that only wild type galectin-3 undergoes phosphorylation in vivo. Expression of Ser(6) mutants of galectin-3 failed to protect cells from cisplatin-induced cell death and poly(ADP-ribose) polymerase from degradation when compared with wild type galectin-3. The non-phosphorylated galectin-3 mutants failed to protect cells from anoikis with G(1) arrest when cells were cultured in suspension. In response to a loss of cell-substrate interactions, only cells expressing wild type galectin-3 down-regulated cyclin A expression and up-regulated cyclin D(1) and cyclin-dependent kinase inhibitors, i.e. p21(WAF1/CIP1) and p27(KIP1) expression levels. These results demonstrate that galectin-3 phosphorylation regulates its anti-apoptotic signaling activity.
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PMID:Galectin-3 phosphorylation is required for its anti-apoptotic function and cell cycle arrest. 1172 77