PloS one, 2012-08, Vol.7 (8), p.e41523-e41523
2012
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- Autor(en) / Beteiligte
- Titel
- MicroRNA-7 inhibits epithelial-to-mesenchymal transition and metastasis of breast cancer cells via targeting FAK expression
- Ist Teil von
- PloS one, 2012-08, Vol.7 (8), p.e41523-e41523
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2012
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Focal adhesion kinase (FAK) is an important mediator of extracellular matrix integrin signaling, cell motility, cell proliferation and cell survival. Increased FAK expression is observed in a variety of solid human tumors and increased FAK expression and activity frequently correlate with metastatic disease and poor prognosis. Herein we identify miR-7 as a direct regulator of FAK expression. miR-7 expression is decreased in malignant versus normal breast tissue and its expression correlates inversely with metastasis in human breast cancer patients. Forced expression of miR-7 produced increased E-CADHERIN and decreased FIBRONECTIN and VIMENTIN expression in breast cancer cells. The levels of miR-7 expression was positively correlated with E-CADHERIN mRNA and negatively correlated with VIMENTIN mRNA levels in breast cancer samples. Forced expression of miR-7 in aggressive breast cancer cell lines suppressed tumor cell monolayer proliferation, anchorage independent growth, three-dimensional growth in Matrigel, migration and invasion. Conversely, inhibition of miR-7 in the HBL-100 mammary epithelial cell line promoted cell proliferation and anchorage independent growth. Rescue of FAK expression reversed miR-7 suppression of migration and invasion. miR-7 also inhibited primary breast tumor development, local invasion and metastatic colonization of breast cancer xenografts. Thus, miR-7 expression is decreased in metastatic breast cancer, correlates with the level of epithelial differentiation of the tumor and inhibits metastatic progression.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0041523Titel-ID: cdi_plos_journals_1326222496
- Format
- –
- Schlagworte
- 3' Untranslated Regions, Algorithms, Animals, Base Sequence, Biology, Breast cancer, Breast Neoplasms - genetics, Breast Neoplasms - metabolism, Breast Neoplasms - pathology, Cancer, Cancer cells, Cancer metastasis, Cell adhesion & migration, Cell Line, Tumor, Cell Movement - genetics, Cell Proliferation, Cell survival, Colonization, Correlation, Down-Regulation - genetics, E-cadherin, Epithelial cells, Epithelial-Mesenchymal Transition - genetics, Extracellular matrix, Female, Fibronectin, Fibronectins, Focal adhesion kinase, Focal Adhesion Protein-Tyrosine Kinases - genetics, Gene expression, Gene Expression Regulation, Neoplastic, Growth factors, Humans, Integrins, Kinases, Laboratories, Life sciences, Lymphatic system, Mammary gland, Medicine, Mesenchyme, Metastases, Metastasis, Mice, Mice, Nude, MicroRNA, MicroRNAs, MicroRNAs - genetics, miRNA, mRNA, Neoplasm Metastasis - genetics, Phenotype, Prognosis, Prostate cancer, Ribonucleic acid, RNA, Signaling, Stem cells, Tumor cell lines, Tumors, Vimentin, Xenograft Model Antitumor Assays, Xenografts, Xenotransplantation