Back to Search
Start Over
Targets of the tumor suppressor miR-200 in regulation of the epithelial-mesenchymal transition in cancer.
- Source :
-
Cancer research [Cancer Res] 2011 Dec 15; Vol. 71 (24), pp. 7670-82. Date of Electronic Publication: 2011 Oct 10. - Publication Year :
- 2011
-
Abstract
- The microRNA-200 (miR-200) family restricts epithelial-mesenchymal transition (EMT) and metastasis in tumor cell lines derived from mice that develop metastatic lung adenocarcinoma. To determine the mechanisms responsible for EMT and metastasis regulated by this microRNA, we conducted a global liquid chromatography/tandem mass spectrometry analysis to compare metastatic and nonmetastatic murine lung adenocarcinoma cells which had undergone EMT because of loss of miR-200. An analysis of syngeneic tumors generated by these cells identified multiple novel proteins linked to metastasis. In particular, the analysis of conditioned media, cell surface proteins, and whole-cell lysates from metastatic and nonmetastatic cells revealed large-scale modifications in the tumor microenvironment. Specific increases were documented in extracellular matrix (ECM) proteins, peptidases, and changes in distribution of cell adhesion proteins in the metastatic cell lines. Integrating proteomic data from three subproteomes, we defined constituents of a multilayer protein network that both regulated and mediated the effects of TGFβ. Lastly, we identified ECM proteins and peptidases that were directly regulated by miR-200. Taken together, our results reveal how expression of miR-200 alters the tumor microenvironment to inhibit the processes of EMT and metastasis.
- Subjects :
- Adenocarcinoma genetics
Adenocarcinoma metabolism
Adenocarcinoma pathology
Animals
Blotting, Western
Carcinoma, Non-Small-Cell Lung genetics
Carcinoma, Non-Small-Cell Lung metabolism
Carcinoma, Non-Small-Cell Lung pathology
Cell Line, Tumor
Chromatography, Liquid
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks
Genes, Tumor Suppressor
Humans
Lung Neoplasms genetics
Lung Neoplasms metabolism
Lung Neoplasms pathology
Mice
Neoplasm Metastasis
Neoplasms pathology
Oligonucleotide Array Sequence Analysis
Proteomics methods
Signal Transduction
Tandem Mass Spectrometry
Transforming Growth Factor beta genetics
Transforming Growth Factor beta metabolism
Tumor Microenvironment genetics
Epithelial-Mesenchymal Transition genetics
MicroRNAs genetics
Neoplasms genetics
Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1538-7445
- Volume :
- 71
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- Cancer research
- Publication Type :
- Academic Journal
- Accession number :
- 21987723
- Full Text :
- https://doi.org/10.1158/0008-5472.CAN-11-0964