N-cadherin mediates angiogenesis by regulating monocyte chemoattractant protein-1 expression via PI3K/Akt signaling in prostate cancer cells

Exp Cell Res. 2011 Oct 15;317(17):2512-21. doi: 10.1016/j.yexcr.2011.07.024. Epub 2011 Aug 9.


Over the past decade, evidence continues to mount showing that N-cadherin is a critical protein in cancer progression and metastasis. In the present study, we evaluated the expression of N-cadherin in human prostate cancer tissue specimens and cell lines. Enhanced expression of N-cadherin was observed in both the malignant and bone-metastasized prostate tissue specimens compared to the healthy prostate tissues. Consistent with the tissue array data, N-cadherin was highly expressed in PC3, but not in Du145 and LNCaP human prostate cell lines. Based on cell to cell binding assay, we found that N-cadherin expression facilitates homotypic interaction between human prostate cancer cells and human microvascular endothelial cells (HMEC). Human angiogenesis antibody array and in vitro angiogenesis assay showed that siRNA-mediated knockdown of N-cadherin reduced the secretion of monocyte chemoattractant protein-1 (MCP-1), which played a potential role in stimulating capillary network formation of HMEC. Additionally, culture supernatant of Du145 cells transfected with full-length N-cadherin expressing plasmid showed increased MCP-1 expression and chemoattractant ability compared to normal Du145 cells. Further, we noticed that blocking PI3K activity inhibited N-cadherin mediated MCP-1 expression. Our data demonstrated that N-cadherin in prostate cancer cell mediates cell-cell adhesion and regulates MCP-1 expression via the PI3K/Akt signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / biosynthesis
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Cadherins / biosynthesis
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Cell Adhesion
  • Cells, Cultured
  • Chemokine CCL2 / biosynthesis*
  • Chemokine CCL2 / metabolism
  • Humans
  • Male
  • Neovascularization, Pathologic / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction*


  • Antigens, CD
  • CDH2 protein, human
  • Cadherins
  • Chemokine CCL2
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt