Description:
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.
Advantages
·
Stage
specificity
·
Two
novel secreted proteins as potential inhibitors of metastasis
Applications
·
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
Background
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.
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 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.
Contact:
Laurie
Tzodikov
Princeton
University Office of Technology Licensing ¿ (609) 258-7256¿ tzodikov@princeton.edu
Shan
Wan
Princeton
University Office of Technology Licensing ¿ (609) 258-5579¿ shanwan@princeton.edu