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.
Publications:
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
tzodikov@princeton.edu