TY - JOUR
T1 - Cadherin-11 in poor prognosis malignancies and rheumatoid arthritis
T2 - Common target, common therapies
AU - Assefnia, Shahin
AU - Dakshanamurthy, Sivanesan
AU - Auvil, Jaime M.Guidry
AU - Hampel, Constanze
AU - Anastasiadis, Panos Z.
AU - Kallakury, Bhaskar
AU - Uren, Aykut
AU - Foley, David W.
AU - Brown, Milton L.
AU - Shapiro, Lawrence
AU - Brenner, Michael
AU - Haigh, David
AU - Byers, Stephen W.
PY - 2014
Y1 - 2014
N2 - 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 basallike 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.
AB - 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 basallike 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.
KW - Breast cancer
KW - Cadherin-11
KW - Celecoxib
KW - Glioblastoma
KW - Rheumatoid arthritis
KW - Small molecule inhibitor
UR - http://www.scopus.com/inward/record.url?scp=84904251524&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84904251524&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.1538
DO - 10.18632/oncotarget.1538
M3 - Article
C2 - 24681547
AN - SCOPUS:84904251524
SN - 1949-2553
VL - 5
SP - 1458
EP - 1474
JO - Oncotarget
JF - Oncotarget
IS - 6
ER -