Cadherin-11 in poor prognosis malignancies and rheumatoid arthritis: common target, common therapies

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// Shahin Assefnia 1,* , Sivanesan Dakshanamurthy 1,* , Jaime M. Guidry Auvil 1,* , Constanze Hampel 1 , Panos Z. Anastasiadis 2 , Bhaskar Kallakury 1 , Aykut Uren 1 , David W Foley 4 , Milton L. Brown 5 , Lawrence Shapiro 6 , Michael Brenner 3 , David Haigh 4 and Stephen W. Byers 1 1 The Georgetown-Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, USA 2 Department of Cancer Cell Biology, Mayo Clinic, Jacksonville, FL, USA 3 Department of Medicine, Division of Rheumatology, Immunology, and Allergy, Brigham and Women’s Hospital, Boston, MA. USA 4 Center for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical sciences, Queen’s University Belfast, Northern Ireland, UK 5 Center for Drug Discovery, Georgetown University Medical Center,Washington, DC, USA 6 Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA * These authors contributed equally Correspondence: Stephen W. Byers, email: // Keywords : cadherin-11, breast cancer, glioblastoma, small molecule inhibitor, rheumatoid arthritis, celecoxib Received : October 26, 2013 Accepted : November 14, 2013 Published : November 15, 2013 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.