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

Zhang J, Park SI, Artime MC, Summy JM, Shah AN, Bomser JA, Dorfleutner A, Flynn DC, Gallick GE
J Clin Invest. 2007 117 (10): 2962-73

PMID: 17885682 · PMCID: PMC1978423 · DOI:10.1172/JCI30710

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

MeSH Terms (21)

Animals Carcinoma Cell Adhesion Cell Line, Tumor Cell Movement Cell Proliferation Cell Transformation, Neoplastic Down-Regulation Extracellular Matrix Focal Adhesions Humans Integrins Male Mice Mice, Nude Microfilament Proteins Mutation Phosphoproteins Prostatic Neoplasms Protein-Tyrosine Kinases Up-Regulation

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