@article {671,
	title = {The cancer glycocalyx mechanically primes integrin-mediated growth and survival.},
	journal = {Nature},
	volume = {511},
	year = {2014},
	month = {2014 Jul 17},
	pages = {319-25},
	abstract = {<p>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.</p>
},
	keywords = {Animals, Breast, Cell Line, Tumor, Cell Proliferation, Cell Survival, Fibroblasts, Glycocalyx, Glycoproteins, Humans, Immobilized Proteins, Integrins, Mice, Molecular Targeted Therapy, Mucin-1, Neoplasm Metastasis, Neoplasms, Neoplastic Cells, Circulating, Protein Binding, Receptors, Cell Surface},
	issn = {1476-4687},
	doi = {10.1038/nature13535},
	author = {Paszek, Matthew J and DuFort, Christopher C and Rossier, Olivier and Bainer, Russell and Mouw, Janna K and Godula, Kamil and Hudak, Jason E and Lakins, Jonathon N and Wijekoon, Amanda C and Cassereau, Luke and Rubashkin, Matthew G and Magbanua, Mark J and Thorn, Kurt S and Davidson, Michael W and Rugo, Hope S and Park, John W and Hammer, Daniel A and Giannone, Gr{\'e}gory and Bertozzi, Carolyn R and Weaver, Valerie M}
}
@article {351,
	title = {HOXA9 regulates BRCA1 expression to modulate human breast tumor phenotype.},
	journal = {J Clin Invest},
	volume = {120},
	year = {2010},
	month = {2010 May},
	pages = {1535-50},
	abstract = {<p>Breast cancer 1, early onset (BRCA1) expression is often reduced in sporadic breast tumors, even in the absence of BRCA1 genetic modifications, but the molecular basis for this is unknown. In this study, we identified homeobox A9 (HOXA9) as a gene frequently downregulated in human breast cancers and tumor cell lines and noted that reduced HOXA9 transcript levels associated with tumor aggression, metastasis, and patient mortality. Experiments revealed that loss of HOXA9 promoted mammary epithelial cell growth and survival and perturbed tissue morphogenesis. Restoring HOXA9 expression repressed growth and survival and inhibited the malignant phenotype of breast cancer cells in culture and in a xenograft mouse model. Molecular studies showed that HOXA9 restricted breast tumor behavior by directly modulating the expression of BRCA1. Indeed, ectopic expression of wild-type BRCA1 phenocopied the tumor suppressor function of HOXA9, and reducing BRCA1 levels or function inhibited the antitumor activity of HOXA9. Consistently, HOXA9 expression correlated with BRCA1 in clinical specimens and with tumor aggression in patients lacking estrogen receptor/progesterone receptor expression in their breast tissue. These findings indicate that HOXA9 restricts breast tumor aggression by modulating expression of the tumor suppressor gene BRCA1, which we believe provides an explanation for the loss of BRCA1 expression in sporadic breast tumors in the absence of BRCA1 genetic modifications.</p>
},
	keywords = {Adult, Animals, BRCA1 Protein, Breast Neoplasms, Female, Gene Expression Regulation, Neoplastic, Homeodomain Proteins, Humans, Mice, Middle Aged, Models, Genetic, Neoplasm Transplantation, Phenotype, Receptors, Estrogen, Receptors, Progesterone, Treatment Outcome},
	issn = {1558-8238},
	doi = {10.1172/JCI39534},
	author = {Gilbert, Penney M and Mouw, Janna K and Unger, Meredith A and Lakins, Johnathon N and Gbegnon, Mawuse K and Clemmer, Virginia B and Benezra, Miriam and Licht, Jonathan D and Boudreau, Nancy J and Tsai, Kelvin K C and Welm, Alana L and Feldman, Michael D and Weber, Barbara L and Weaver, Valerie M}
}
