Targeting alpha B-Crystallin in Basal-like Breast Cancer - Breast Cancer Research Foundation

Basal-like tumors are a newly recognized type of breast cancer which are clinically aggressive and lack targeted therapies because they are estrogen receptor (ER)-negative and HER2-negative. Dr. Cryns and colleagues have shown that a cell stress protein called αB-crystallin contributes to the aggressive behavior of basal-like tumors in part by making them resistant to chemotherapy. Dr. Cryns and coworkers have developed new in vivo models of basal-like breast cancer that spread (“metastasize”) from the breast to the brain, lungs and other organs. During the current BCRF project period, Dr. Cryns and his team have demonstrated that αBcrystallin promotes brain metastasis by enhancing the adhesion of breast cancer cells to cells that make up blood vessels in the brain and by facilitating penetration of the blood-brain barrier (BBB). The team has also demonstrated that αB-crystallin is a key regulator of breast cancer metastasis by preventing cell death that normally occurs when tumor cells detach from surrounding cells in the breast and escape into the bloodstream, an early step in metastasis. Taken together, these studies point to αB-crystallin as an important molecular regulator of metastasis in basal-like breast cancer and a promising drug target for these poor prognosis breast tumors.