AFAP-110 is overexpressed in prostate cancer and contributes to tumorigenic growth by regulating focal contacts.

摘要: The actin filament-associated protein AFAP-110 is an cross-linking first identified as a substrate of the viral oncogene v-Src. regulates cytoskeleton integrity but also functions adaptor that affects crosstalk between Src and PKC. Here we investigated roles in tumorigenic process prostate carcinoma. Using immunohistochemistry human tissue arrays, found was absent or expressed at very low levels normal prostatic epithelium benign hyperplasia significantly increased carcinomas. level carcinomas correlated with Gleason scores. Downregulation PC3 cancer cells inhibited cell proliferation vitro tumorigenicity growth orthotopic nude mouse models. Furthermore, downmodulation resulted decreased cell-matrix adhesion migration, defective focal adhesions, reduced integrin beta1 expression. Reintroduction avian mutant disabling its interaction restored these properties. However, expression lacking PKC-interacting domain failed to restore properties parental cells. Thus, associated progressive stages critical for growth, part by regulating contacts PKC-dependent mechanism.