miR-200 Family and miR194/192 Cluster of miRNAs in Cancer Progression and Metastasis

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Princeton University Invention # 09-2551



Over 90% of cancer-related deaths are due to the metastatic spread of primary tumor cells to distant vital organs. Epithelial-mesenchymal transition (EMT) is a key cellular process through which tumor cells gain the ability to migrate and invade into their surrounding tissue. The reverse process, (MET), has also been postulated to be important for tumor cells to regain their epithelial phenotype once they reach the target organ and to successfully produce macroscopic lesions. MicroRNAs (miRNAs) have been increasingly recognized to play important roles in normal physiology and in pathological processes, including cancer and metastasis.


Studies by researchers in Molecular Biology, Princeton University have identified two classes of miRNAs, the miR-200 family and the miR-194/192 cluster, that hinder EMT and promote the MET process. These miRNAs maintain the epithelial phenotype and inhibit EMT by repressing the expression of transcriptional inhibitors of E-cadherin, including ZEB1/ZEB2 and MeCP2 respectively. Overexpression of these miRNAs inhibits TGFβ-induced EMT in normal mammary epithelial cells. Furthermore, ectopic expression of the EMT-related miRNAs in invasive breast tumor cells induces MET, with a corresponding reduction in migration and invasion. Surprisingly, it was also found that elevated miR-200 expression is correlated with the increased ability of tumor cells to generate macroscopic lesions at secondary metastasis sites. High miR-200 expression is correlated with reduced recurrence-free survival in clinical samples, supporting the role of miR-200s in enhancing metastasis formation. These data in aggregate suggest a stage-specific role of these miRNAs in metastasis. In vivo metastasis assays and spontaneous metastasis assays confirm the stage-specific function of the miR-200 family in tumor progression.


These miRNAs may serve as master regulators of the transition between epithelial and mesenchymal states of tumor cells and play important roles in both the initial invasion of primary tumors as well as metastatic colonization of secondary target organs, and may serve as potentially new agents of anti-metastasis therapeutics. 


Princeton is currently seeking commercial partners for the further development and commercialization of this opportunity. Patent protection is pending.




Korpal M, Lee LS, Hu G, Kang y, y JB, Tkačik G, Callan CG, The miR-200 Family  Inhibits Epithelial-Mesenchymal Transition and Cancer Cell  Migration by Direct Targeting of E-cadherin Transciptional Repressors ZEB1 and ZEB2, Jounrnal of Biological Chemistry, Vol 283, 22, May 30th 2008, 14910-14914.


For more information on Princeton University invention # 09-2551 please contact:


                        Laurie Tzodikov

                        Office of Technology Licensing and Intellectual Property

                        Princeton University

                        4 New South Building

                        Princeton, NJ 08544-0036

                        (609) 258-7256

                        (609) 258-1159 fax


Patent Information:
For Information, Contact:
Laurie Tzodikov
Licensing Associates
Princeton University
Yibin Kang
Manav Korpal