Novel Therapeutics for Cancer Metastasis

Web Published:

Princeton Docket # 11-2691-1

Using various in vitro and in vivo xenograft model systems and clinical samples, researchers in the department of molecular biology, Princeton University have validated a stage-specific functional role of the miR-200 family to tumor progression.  Current studies suggest that the miR-200 family may hinder an early step of metastasis (invasion) but yet can promote metastatic colonization in a distant organ, a critical rate-limiting step in the multiple-step cascade of metastasis. These studies suggest that the miR-200 family may play a key role to allow the ability for tumor cells to switch between two bistable states (transient mesenchymal phenotype for invasion, and epithelial phenotype for primary tumor growth and metastatic expansion in secondary organ).  Targeting these miRNAs might be important for therapeutic intervention of invasion/metastasis in a stage-specific manner.  Furthermore, two potent secreted metastasis suppressor proteins have been identified as targets of the miR-200 pathway at the stage of lung colonization.  These proteins could potentially be developed as inhibitors of clinical metastasis to bypass the biphasic role of miR-200s to inhibit invasion but promote colonization. 


 ·         Stage specificity

·         Two novel secreted proteins as potential inhibitors of metastasis


·         Metastasis therapy by modulating miR-200s in a stage-specific manner

·         Metastasis therapy by administrating recombinant metastasis inhibitory proteins

·         miR-200s as diagnostic markers for metastasis progression

·         miR-200s as predictive markers and targets for therapeutic intervention


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. Our studies have identified the miR-200 family miRNAs that hinder EMT and invasion but promote the MET and metastatic colonization, in part by targeting the Sec23a-dependent secretion of two metastasis suppressive proteins: IGFBP4 and TINAGL1.


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 Transcriptional Repressors ZEB1 and ZEB2, Journal of Biological Chemistry, Vol 283, 22, May 30th 2008, 14910-14914.

Korpal M, Ell BJ, Buffa FM, Ibrahim T, Terrasa AC, Mercatali L, Khan Z, Blanco MA, Goodarzi H, Hua Y, Wei Y, Hu G, Garcia B, Ragoussis J, Amadori D, Harris AL, and Kang Y. (2011) Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization. Nature Medicine, 2011 Aug 7;17(9):1101-8.

The Inventor

Yibin Kang is an associate professor of molecular biology. The central theme of his research is a multidisciplinary and integrative approach to the analysis of the molecular basis of cancer metastasis, combining molecular biology and genomics tools with animal models and advanced in vivo imaging technologies. His work is focused on the identification of metastasis genes and functional characterization of their involvement in tumor-stromal interactions during the formation of metastasis in different organs and is also interested in regulators of mammary gland development and early oncogenic events that may have significant impact on tumor progression and metastasis. 

Intellectual Property & Development status

Patent protection is pending. 

Princeton University is interested in identifying industrial collaborators to further develop these biomarkers and inhibitors.


Laurie Tzodikov

Princeton University Office of Technology Licensing ¿ (609) 258-7256¿

Shan Wan

Princeton University Office of Technology Licensing ¿ (609) 258-5579¿

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