| First Author | Paszek MJ | Year | 2014 |
| Journal | Nature | Volume | 511 |
| Issue | 7509 | Pages | 319-25 |
| PubMed ID | 25030168 | Mgi Jnum | J:213709 |
| Mgi Id | MGI:5585660 | Doi | 10.1038/nature13535 |
| Citation | Paszek MJ, et al. (2014) The cancer glycocalyx mechanically primes integrin-mediated growth and survival. Nature 511(7509):319-25 |
| abstractText | 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. |
