Cysteine-linked dimerization of BST-2 confers anoikis resistance to breast cancer cells by negating proapoptotic activities to promote tumor cell survival and growth.

ABSTRACT: Almost all breast tumors express the antiviral protein BST-2 with 67%, 25% and 8.2% containing high, medium or low levels of BST-2, respectively. Breast tumor cells and tissues that contain elevated levels of BST-2 are highly aggressive. Suppression of BST-2 expression reprograms tumorigenic properties of cancer cells and diminishes cancer cell aggressiveness. Using structure/function studies, we report that dimerization of BST-2 through cysteine residues located in the BST-2 extracellular domain (ECD), leads to anoikis resistance and cell survival through proteasome-mediated degradation of BIM-a key proapoptotic factor. Importantly, BST-2 dimerization promotes tumor growth in preclinical breast cancer models in vitro and in vivo. Furthermore, we demonstrate that restoration of the ECD cys

SUBMITTER: Mahauad-Fernandez WD 

PROVIDER: S-EPMC5386562 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature