@article {256,
	title = {Oncogenic targeting of BRM drives malignancy through C/EBPβ-dependent induction of α5 integrin.},
	journal = {Oncogene},
	year = {2013},
	month = {2013 Jun 17},
	abstract = {<p>Integrin expression and activity are altered in tumors, and aberrant integrin signaling promotes malignancy. However, how integrins become altered in tumors remains poorly understood. We discovered that oncogenic activation of MEK signaling induces cell growth and survival, and promotes the malignant phenotype of mammary epithelial cells (MECs) by increasing α5 integrin expression. We determined that MEK activates c-Myc to reduce the transcription of the SWI/SNF chromatin remodeling enzyme Brahma (BRM). Our studies revealed that reduced BRM expression and/or activity drives the malignant behavior of MECs by epigenetically promoting C/EBPβ expression to directly induce α5 integrin transcription. Consistently, we could show that restoring BRM levels normalized the malignant behavior of transformed MECs in culture and in vivo by preventing C/EBPβ-dependent α5 integrin transcription. Our findings identify a novel mechanism whereby oncogenic signaling promotes malignant transformation by regulating transcription of a key chromatin remodeling molecule that regulates integrin-dependent stromal-epithelial interactions.Oncogene advance online publication, 17 June 2013; doi:10.1038/onc.2013.220.</p>
},
	issn = {1476-5594},
	doi = {10.1038/onc.2013.220},
	author = {Damiano, L and Stewart, K M and Cohet, N and Mouw, J K and Lakins, J N and Debnath, J and Reisman, D and Nickerson, J A and Imbalzano, A N and Weaver, V M}
}
@article {556,
	title = {Tissue phenotype depends on reciprocal interactions between the extracellular matrix and the structural organization of the nucleus.},
	journal = {Proc Natl Acad Sci U S A},
	volume = {95},
	year = {1998},
	month = {1998 Dec 8},
	pages = {14711-6},
	abstract = {<p>What determines the nuclear organization within a cell and whether this organization itself can impose cellular function within a tissue remains unknown. To explore the relationship between nuclear organization and tissue architecture and function, we used a model of human mammary epithelial cell acinar morphogenesis. When cultured within a reconstituted basement membrane (rBM), HMT-3522 cells form polarized and growth-arrested tissue-like acini with a central lumen and deposit an endogenous BM. We show that rBM-induced morphogenesis is accompanied by relocalization of the nuclear matrix proteins NuMA, splicing factor SRm160, and cell cycle regulator Rb. These proteins had distinct distribution patterns specific for proliferation, growth arrest, and acini formation, whereas the distribution of the nuclear lamina protein, lamin B, remained unchanged. NuMA relocalized to foci, which coalesced into larger assemblies as morphogenesis progressed. Perturbation of histone acetylation in the acini by trichostatin A treatment altered chromatin structure, disrupted NuMA foci, and induced cell proliferation. Moreover, treatment of transiently permeabilized acini with a NuMA antibody led to the disruption of NuMA foci, alteration of histone acetylation, activation of metalloproteases, and breakdown of the endogenous BM. These results experimentally demonstrate a dynamic interaction between the extracellular matrix, nuclear organization, and tissue phenotype. They further show that rather than passively reflecting changes in gene expression, nuclear organization itself can modulate the cellular and tissue phenotype.</p>
},
	keywords = {Cell Nucleus, Extracellular Matrix, Extracellular Matrix Proteins, Female, Gene Expression Regulation, Humans, Morphogenesis, Nuclear Proteins, Tumor Cells, Cultured},
	issn = {0027-8424},
	author = {Leli{\`e}vre, S A and Weaver, V M and Nickerson, J A and Larabell, C A and Bhaumik, A and Petersen, O W and Bissell, M J}
}
