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Cadherin-11 in poor prognosis malignancies and rheumatoid arthritis: common target,common therapies
Authors:Shahin Assefnia  Sivanesan Dakshanamurthy  Jaime M. Guidry Auvil  Constanze Hampel  Panos Z. Anastasiadis  Bhaskar Kallakury  Aykut Uren  David W Foley  Milton L. Brown  Lawrence Shapiro  Michael Brenner  David Haigh  Stephen W. Byers
Abstract:Cadherin-11 (CDH11), associated with epithelial to mesenchymal transformation in development, poor prognosis malignancies and cancer stem cells, is also a major therapeutic target in rheumatoid arthritis (RA). CDH11 expressing basal-like breast carcinomas and other CDH11 expressing malignancies exhibit poor prognosis. We show that CDH11 is increased early in breast cancer and ductal carcinoma in-situ. CDH11 knockdown and antibodies effective in RA slowed the growth of basal-like breast tumors and decreased proliferation and colony formation of breast, glioblastoma and prostate cancer cells. The repurposed arthritis drug celecoxib, which binds to CDH11, and other small molecules designed to bind CDH11 without inhibiting COX-2 preferentially affect the growth of CDH11 positive cancer cells in vitro and in animals. These data suggest that CDH11 is important for malignant progression, and is a therapeutic target in arthritis and cancer with the potential for rapid clinical translation
Keywords:cadherin-11   breast cancer   glioblastoma   small molecule inhibitor   rheumatoid arthritis   celecoxib
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