The Emerging Role of Galectins and O-GlcNAc Homeostasis in Processes of Cellular Differentiation

Abstract

Galectins are a family of soluble β-galactoside-binding proteins with diverse glycan-dependent and glycan-independent functions outside and inside the cell. Human cells express twelve out of sixteen recognized mammalian galectin genes and their expression profiles are very different between cell types and tissues. In this review, we summarize the current knowledge on the changes in the expression of individual galectins at mRNA and protein levels in different types of differentiating cells and the effects of recombinant galectins on cellular differentiation. A new model of galectin regulation is proposed considering the change in O-GlcNAc homeostasis between progenitor/stem cells and mature differentiated cells. The recognition of galectins as regulatory factors controlling cell differentiation and self-renewal is essential for developmental and cancer biology to develop innovative strategies for prevention and targeted treatment of proliferative diseases, tissue regeneration, and stem-cell therapy.

The glycobiological landscape of breast cancer: insights into galectins and O-GlcNAc homeostasis-related genes

“…The goal of this study was to analyse the glycobiological landscape of breast cancer using the TCGA dataset and focusing on genes encoding O-GlcNAc cycle enzymes and galectins. These systems represent two different pools of cellular molecules involved in protein glycosylation and glycan recognition and their coordinated functions have been proposed to control processes of cell differentiation and self-renewal [18,19], which are relevant to cancer development and progression.…”

“…Dysregulation of O-GlcNAc homeostasis (elevation of O-GlcNAc levels) has been observed in many cancers including breast tumors [20,21], and in association with a variety of cellular and organismal stress responses [22][23][24]. Noteworthy, high O-GlcNAc is also a feature of undifferentiated and stem cells [19] that provides a context for studying the cell stemness-related transcription factors expressed in cancer cells [25]. However, our current knowledge about functional associations between O-GlcNAc homeostasis-regulating genes and relevant galectin/stemness-related markers in cancer is very scarсe.…”

“…Many intracellular proteins can be O-GlcNAcylated that results in changes of gene expression, enzymatic activity, and localization of responsive proteins [14][15][16]. The latter aspect is especially important for galectins, which have been recently proposed to release from or accumulate in cells depending on O-GlcNAc homeostasis [17][18][19]. Dysregulation of O-GlcNAc homeostasis (elevation of O-GlcNAc levels) has been observed in many cancers including breast tumors [20,21], and in association with a variety of cellular and organismal stress responses [22][23][24].…”

Functions and Inhibition of Galectin-7, an Emerging Target in Cellular Pathophysiology

“…This dysregulation of galectin-7 causes a significant reduction of keratinocyte migration and thus, improper wound healing [ 24 ]. The context of this dysregulation can be associated with O -GlcNAc-mediated processes controlling cellular differentiation [ 25 ]. A more detailed review regarding the re-epithelialization of skin wounds is reported [ 26 ].…”

Expression, Regulation, and Functions of the Galectin-16 Gene in Human Cells and Tissues

“…Galectins comprise a family of soluble β-galactoside binding proteins, which regulate key biological processes including cell growth, differentiation, apoptosis, and immune responses [ 1 , 2 , 3 , 4 ]. Sixteen galectin genes have been identified in animal kingdoms, 12 of which are expressed in humans.…”