期刊
NATURE
卷 511, 期 7509, 页码 319-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature13535
关键词
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资金
- Kavli Institute
- UCSF Program for Biomedical Breakthrough postdoctoral fellowships
- DoD NDSEG Fellowship
- NIH Pathway to Independence Award [K99 EB013446-02]
- French Ministry of Research
- CNRS
- ANR grant Nanomotility
- INSERM
- Fondation ARC pour la Recherche sur le Cancer
- Conseil Regional Aquitaine
- NIH [AI082292-03A1, 2R01GM059907-13, GM59907]
- Breast Cancer Research Foundation
- BCRP DOD Era of Hope Scholar Expansion grant [BC122990]
- NIH NCI [U54CA163155-01, U54CA143836-01, 1U01 E5019458-01, CA138818-01A1]
- France BioImaging [ANR-10-INBS-04-01]
- CDMRP [542337, BC122990] Funding Source: Federal RePORTER
Malignartcy is associated with altered expression of glycans and glycoprotems that contribute 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.
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