The cancer glycocalyx mechanically primes integrin-mediated growth and survival
By Matthew J. Paszek, Christopher C DuFort, O. Rossier, Russell Bainer, J. Mouw, K. Godula, J. Hudak, J. Lakins, Amanda C. Wijekoon, L. Cassereau and 10 more. Nature, 2014
636 citations recorded by the source corpus.
Malignancy is associated with altered expression of glycans and glycoproteins that contribute to the cellular glycocalyx. We constructed a glycoprotein expression signature, which revealed that metastatic tumours upregulate expression of bulky glycoproteins. A computational model predicted that these glycoproteins would influence transmembrane receptor spatial organization and function. We tested this prediction by investigating whether bulky glycoproteins in the glycocalyx promote a tumour phenotype in human cells by increasing integrin adhesion and signalling. Our data revealed that a bulky glycocalyx facilitates integrin clustering by funnelling active integrins into adhesions and altering integrin state by applying tension to matrix-bound integrins, independent of actomyosin contractility. Expression of large tumour-associated glycoproteins in non-transformed mammary cells promoted focal adhesion assembly and facilitated integrin-dependent growth factor signalling to support cell growth and survival. Clinical studies revealed that large glycoproteins are abundantly expressed on circulating tumour cells from patients with advanced disease. Thus, a bulky glycocalyx is a feature of tumour cells that could foster metastasis by mechanically enhancing cell-surface receptor function.
Subfields: Cell Biology, Molecular Biology, Physiology
View Paper: https://www.semanticscholar.org/paper/8df9949894e17037df6e317493493130325100e0
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Citations in the corpus
- Biological roles of glycans (2016, background): “Since a bulky glycocalyx is a feature of malignant cells, it is suggested that these features could foster the spread of cancer by mechanically enhancing cell surface receptor function (545).”
- Integrin Signaling in Cancer: Mechanotransduction, Stemness, Epithelial Plasticity, and Therapeutic Resistance (2019, background): “Moreover, invasive cancer cells often bear bulky glycoproteins on their surface, which create an incompressible ring around integrins and hence increase the tensile force applied to integrin ligand bonds, facilitating integrin clustering and signaling (Paszek et al., 2014).”