Targets of the tumor suppressor miR-200 in regulation of the epithelial-mesenchymal transition in cancer.
Targets of the tumor suppressor miR-200 in regulation of the epithelial-mesenchymal transition in cancer.
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DOI：
10.1158/0008-5472.can-11-0964
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发表时间：
2011-12-15
期刊：
影响因子：
11.2
通讯作者：
Hanash SM
中科院分区：
文献类型：
--
作者：
Schliekelman MJ;Gibbons DL;Faca VM;Creighton CJ;Rizvi ZH;Zhang Q;Wong CH;Wang H;Ungewiss C;Ahn YH;Shin DH;Kurie JM;Hanash SM
The microRNA-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 LC-MS/MS analysis to compare metastatic and non-metastatic murine lung adenocarcinoma cells which had undergone EMT due to 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 non-metastatic cells revealed large scale modifications in the tumor microenvironment. Specific increases were documented in extracellular matrix proteins, peptidases, and changes in distribution of cell adhesion proteins in the metastatic cell lines. Integrating proteomic data from three sub-proteomes, we defined constituents of a multilayer protein network that both regulated and mediated the effects of transforming growth factor TGFβ. Lastly, we identified extracellular matrix 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.
