Cancer: Sugar-coated cell signalling
Andrew J. Ewald & Mikala Egeblad

Nature (2014) doi:10.1038/nature13506

Cell membranes are covered with sugar-conjugated proteins. New findings suggest that the physical properties of this coating, which is more pronounced in cancer cells, regulate cell survival during tumour spread.

The cell membrane serves as a signalling interface that allows cells to exchange information with their environment. It is constructed from lipids and contains both transmembrane and lipid-tethered proteins, which can be further modified through the covalent addition of sugars to build glycoproteins. Cancer cells frequently have higher levels of glycoproteins, such as mucin-1 (refs 1,2,3), than do healthy cells, and individual glycoproteins can transduce environmental signals that directly promote malignancy. However, glycoproteins also collectively organize into a glycocalyx. In a paper published on Nature's website today, Paszek et al.4 show how the physical properties of this coating regulate the clustering of cell-surface receptors and thereby affect intracellular signalling in ways that can contribute to cancer metastasis.

The authors demonstrate that the thickness of the glycocalyx is a crucial determinant of the spatial and temporal features of receptor–ligand interactions. Specifically, they find that the thick glycocalyx of cancer cells serves as a 'kinetic trap', generating regions on the cell surface where the likelihood of receptor–ligand interactions is increased, driving receptor clustering (Fig. 1). Integrins are transmembrane receptors that bind extracellular matrix (ECM) proteins and are key interpreters and integrators of both the biochemical composition and the mechanical properties of the extracellular space5, 6. Paszek and colleagues reveal that cells with a thick glycocalyx are more efficient at receiving cell-survival signals through integrins, owing to the kinetic-trap properties of the glycocalyx. This may facilitate metastatic spread by enabling cancer cells to survive in the varied tissue and fluid environments they must traverse to colonize distant organs.

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