AFAP-110 is overexpressed in prostate cancer and contributes to tumorigenic growth by regulating focal contacts
Open Access
- 1 October 2007
- journal article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 117 (10), 2962-2973
- https://doi.org/10.1172/jci30710
Abstract
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 β1 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.This publication has 48 references indexed in Scilit:
- AFAP‐110 is required for actin stress fiber formation and cell adhesion in MDA‐MB‐231 breast cancer cellsJournal of Cellular Physiology, 2007
- Prostate cancer stem cellsEuropean Journal of Cancer, 2006
- Src activation of Stat3 is an independent requirement from NF-κB activation for constitutive IL-8 expression in human pancreatic adenocarcinoma cellsAngiogenesis, 2006
- Genistein modulates prostate epithelial cell proliferation via estrogen- and extracellular signal-regulated kinase-dependent pathwaysThe Journal of Nutritional Biochemistry, 2006
- MUC1, MUC2, MUC4, MUC5AC and MUC6 Expression in the Progression of Prostate CancerClinical & Experimental Metastasis, 2005
- Clinging to life: cell to matrix adhesion and cell survivalCancer and Metastasis Reviews, 2005
- β 1 integrin function in vivo: Adhesion, migration and moreCancer and Metastasis Reviews, 2005
- Protein kinase C-α mediates epidermal growth factor receptor transactivation in human prostate cancer cellsMolecular Cancer Therapeutics, 2005
- Integrin–protein kinase C relationshipsBiochemical Society Transactions, 2003
- Characterization of integrin subunits, cellular adhesion and tumorgenicity of four human prostate cell linesZeitschrift für Krebsforschung und Klinische Onkologie, 1993