Cadherin-11 depletion in aggressive MDA-MB-231 breast cancer cells.

Cadherin-11 expression is associated with tumor progression and metastasis in various cancers, including basal-like breast carcinoma and advanced prostate cancer, and invasive cell lines, yet is absent in normal epithelium. We now show cadherin-11 attenuation in aggressive breast and prostate cancer cells results in marked decreases in proliferation, migration, and invasion. Cadherin-11 depletion in MDA-231 cells prevents tumor growth in mice and alters gene expression associated with poor prognosis malignancies. Additionally, a novel small molecule inhibitor targeting its unique adhesive interface significantly inhibits the growth and migration of cadherin-11 positive cells. Cadherin-11 is essential for malignant progression of MDA-231 basal-type cells, and may serve as both an aggressive tumor marker and viable therapeutic target for poor prognosis carcinomas expressing it. Seven microarray samples (3 empty vector controls--RNAi 1B, 4 siRNA treated targeting cadherin-11 wt isoform--RNAi 4A and 6A) were tested in pooled stable siRNA-expressing MDA-MB-231 breast cancer cells to potentially identify significant factors affected when cadherin-11 is depleted in aggressive breast cancer cells. Cadherin-11 appears to play a role in certain poor prognosis, basal-like cancers, however little is known about its regulation. This portion of our study was used to determine what genes may be regulated by cadherin-11 in breast cancer cells, as well as possible insights into mechanisms involved.