Article

Targets of the tumor suppressor miR-200 in regulation of the epithelial-mesenchymal transition in cancer.

Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Cancer Research (impact factor: 7.86). 12/2011; 71(24):7670-82. DOI:10.1158/0008-5472.CAN-11-0964 pp.7670-82
Source: PubMed

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.

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Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

cell adhesion proteins
 
cell surface proteins
 
conditioned media
 
develop metastatic lung adenocarcinoma
 
ECM proteins
 
extracellular matrix
 
global liquid chromatography/tandem mass spectrometry analysis
 
Integrating proteomic data
 
metastatic
 
metastatic cell lines
 
microRNA-200
 
miR-200 alters
 
multilayer protein network
 
multiple novel proteins
 
nonmetastatic cells
 
nonmetastatic murine lung adenocarcinoma cells
 
syngeneic tumors
 
tumor cell lines
 
tumor microenvironment
 
whole-cell lysates