Phosphorylation and changes in the distribution of nucleolin promote tumor metastasis via the PI3K/Akt pathway in colorectal carcinoma

FEBS Lett. 2014 May 21;588(10):1921-9. doi: 10.1016/j.febslet.2014.03.047. Epub 2014 Apr 5.

Abstract

Here, we investigated the molecular mechanism underlying the changes in the distribution of nucleolin. Our study identified PI3K/Akt signaling as an essential pathway regulating the distribution of nucleolin. Furthermore, nucleolin can interact with phospho-PI3K-p55, and changes in the distribution of nucleolin were related to its phosphorylation. Subsequently, we analyzed the correlation of VEGF and nucleolin, and found that distribution of nucleolin related to metastatic potential. Finally, blocking cell surface nucleolin influences the process of epithelial-mesenchymal transitions. This indicates that nucleolin may be a novel cancer therapy target and a predictive marker for tumor migration in colorectal carcinoma.

Keywords: Colorectal carcinoma; Distribution; Metastatic; Nucleolin; PI3K/Akt; VEGF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Line, Tumor
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cell Movement
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Epithelial-Mesenchymal Transition / drug effects
  • Female
  • HCT116 Cells
  • Humans
  • Male
  • Microscopy, Fluorescence
  • Middle Aged
  • Neoplasm Metastasis
  • Nucleolin
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Protein Binding
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA-Binding Proteins / metabolism*
  • Signal Transduction*
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor A / pharmacology

Substances

  • Phosphoproteins
  • RNA-Binding Proteins
  • Vascular Endothelial Growth Factor A
  • Phosphatidylinositol 3-Kinases
  • PIK3R3 protein, human
  • Proto-Oncogene Proteins c-akt