Fibronectin Affects Transient MMP2 Gene Expression through DNA Demethylation Changes in Non-Invasive Breast Cancer Cell Lines

Metastasis accounts for more than 90% of cancer deaths. Cells from primary solid tumors may invade adjacent tissues and migrate to distant sites where they establish new colonies. The tumor microenvironment is now recognized as an important participant in the signaling that induces cancer cell migra...

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Veröffentlicht in:PloS one Jg. 9; H. 9; S. e105806
Hauptverfasser: Pereira, Isabela T., Ramos, Edneia A. S., Costa, Erico T., Camargo, Anamaria A., Manica, Graciele C. M., Klassen, Liliane M. B., Chequin, Andressa, Braun-Prado, Karin, de O. Pedrosa, Fábio, Souza, Emanuel M., Costa, Fabricio F., Klassen, Giseli
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States Public Library of Science 10.09.2014
Public Library of Science (PLoS)
Schlagworte:
Azacitidine - analogs & derivatives
Azacitidine - pharmacology
Base Sequence
Biochemistry
Biology and Life Sciences
Blood vessels
Breast cancer
Breast Neoplasms - pathology
Cancer
Cancer therapies
Cell culture
Cell Line, Tumor
Cell migration
Cell Movement - drug effects
Chromatin
Collagen (type IV)
Degradation
Demethylation
Deoxyribonucleic acid
DNA
DNA methylation
DNA Methylation - drug effects
Epigenetics
Epithelial cells
Extracellular matrix
Fibronectin
Fibronectins - pharmacology
Gelatinase
Gelatinase A
Gene expression
Gene Expression Regulation, Neoplastic - drug effects
Gene Expression Regulation, Neoplastic - genetics
Humans
Matrix Metalloproteinase 2 - genetics
Medical research
Metastases
Metastasis
Molecular biology
Molecular Sequence Data
Neoplasm Invasiveness
Oncology
Pathology
Promoter Regions, Genetic - genetics
Proteins
RNA polymerase
Solid tumors
Stroma
Time Factors
Tissues
Transcriptional Activation - drug effects
Tumor cell lines
Tumor cells
Tumors
Brazil
United States > US
Chicago Illinois
ISSN:1932-6203, 1932-6203
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Zusammenfassung:Metastasis accounts for more than 90% of cancer deaths. Cells from primary solid tumors may invade adjacent tissues and migrate to distant sites where they establish new colonies. The tumor microenvironment is now recognized as an important participant in the signaling that induces cancer cell migration. An essential process for metastasis is extracellular matrix (ECM) degradation by metalloproteases (MMPs), which allows tumor cells to invade local tissues and to reach blood vessels. The members of this protein family include gelatinase A, or MMP-2, which is responsible for the degradation of type IV collagen, the most abundant component of the basal membrane, that separates epithelial cells in the stroma. It is known that fibronectin is capable of promoting the expression of MMP-2 in MCF7 breast cancer cells in culture. In addition, it was already shown that the MMP2 gene expression is regulated by epigenetic mechanisms. In this work, we showed that fibronectin was able to induce MMP2 expression by 30% decrease in its promoter methylation. In addition, a histone marker for an open chromatin conformation was significantly increased. These results indicate a new role for fibronectin in the communication between cancer cells and the ECM, promoting epigenetic modifications.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Competing Interests: The authors have declared that no competing interests exist.
Conceived and designed the experiments: GK ETC FFC. Performed the experiments: EASR ITP GCMM LMBK AC ETC. Analyzed the data: AAC FFC EMS KBP GK. Contributed reagents/materials/analysis tools: AAC EMS FOP. Wrote the paper: ITP EASR ETC FFC FOP GK.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0105806