Anterior gradient protein-2 is a regulator of cellular adhesion in prostate cancer.

Academic Article


  • Anterior Gradient Protein (AGR-2) is reported to be over-expressed in many epithelial cancers and promotes metastasis. A clear-cut mechanism for its observed function(s) has not been previously identified. We found significant upregulation of AGR-2 expression in a bone metastatic prostate cancer cell line, PC3, following culturing in bone marrow-conditioned medium. Substantial AGR-2 expression was also confirmed in prostate cancer tissue specimens in patients with bone lesions. By developing stable clones of PC3 cells with varying levels of AGR-2 expression, we identified that abrogation of AGR-2 significantly reduced cellular attachment to fibronectin, collagen I, collagen IV, laminin I and fibrinogen. Loss of cellular adhesion was associated with sharp decrease in the expression of α4, α5, αV, β3 and β4 integrins. Failure to undergo apoptosis following detachment is a hallmark of epithelial cancer metastasis. The AGR-2-silenced PC3 cells showed higher resistance to Tumor necrosis factor-related apoptosis- inducing ligand (TRAIL) induced apoptosis in vitro. This observation was also supported by significantly reduced Caspase-3 expression in AGR-2-silenced PC3 cells, which is a key effector of both extrinsic and intrinsic death signaling pathways. These data suggest that AGR-2 influence prostate cancer metastasis by regulation of cellular adhesion and apoptosis.
  • Published In

  • PLoS ONE  Journal
  • Keywords

  • Animals, Bone Marrow, Cell Adhesion, Cell Death, Cell Line, Tumor, Cell Movement, Cell Proliferation, Cluster Analysis, Gene Expression, Gene Expression Profiling, Gene Silencing, Humans, Integrins, Male, Mice, Neoplasm Metastasis, Prostatic Neoplasms, Proteins, RNA, Messenger, TNF-Related Apoptosis-Inducing Ligand
  • Digital Object Identifier (doi)

    Author List

  • Chanda D; Lee JH; Sawant A; Hensel JA; Isayeva T; Reilly SD; Siegal GP; Smith C; Grizzle W; Singh R
  • Start Page

  • e89940
  • Volume

  • 9
  • Issue

  • 2