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 tumors 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 a bulky glycocalyx promotes a tumor phenotype by increasing integrin adhesion and signaling. Data revealed that a bulky glycocalyx facilitates integrin clustering by funneling active integrins into adhesions and altering integrin state by applying tension to matrix-bound integrins, independent of actomyosin contractility. Expression of large tumor-associated glycoproteins in non-transformed mammary cells promoted focal adhesion assembly and facilitated integrin-dependent growth factor signaling to support cell growth and survival. Clinical studies revealed that large glycoproteins are abundantly expressed on circulating tumor cells from patients with advanced disease. Thus, a bulky glycocalyx is a feature of tumor cells that could foster metastasis by mechanically enhancing cell surface receptor function.
Matthew J. Paszek, Christopher C. DuFort, Olivier Rossier, Russell Bainer, Janna K. Mouw, Kamil Godula, Jason E. Hudak, Jonathon N. Lakins, Amanda C. Wijekoon, Luke Cassereau, Matthew G. Rubashkin, Mark J. Magbanua, Kurt S. Thorn, Michael W. Davidson, Hope S. Rugo, John W. Park, Daniel A. Hammer, Grégory Giannone, Carolyn R. Bertozzi, Valerie M. Weaver
+ Cf. French abstract on the INSB/CNRS website: