Nogo-B promotes the epithelial-mesenchymal transition in HeLa cervical cancer cells via Fibulin-5

Oncol Rep. 2013 Jan;29(1):109-16. doi: 10.3892/or.2012.2069. Epub 2012 Oct 4.

Abstract

Cervical cancer is a common malignancy in women worldwide, and the occurrence of invasion and metastasis is the major cause for most cancer-related deaths. Epithelial-mesenchymal transition (EMT) has been implicated in the metastasis of primary tumors and provides molecular mechanisms for cervical cancer metastasis. We previously reported that Nogo-B mediates cell motility by binding Fibulin-5. Herein, we show that the increased expression of Nogo-B is correlated with the degree of cervical cancer metastasis. In HeLa cervical cancer cells, overexpression of Nogo-B induces the EMT and promotes cell migration and invasion, while inhibiting cell adhesion. Furthermore, we found that Nogo-B accumulates and co-localizes with Fibulin-5 in pseudopods, and the downstream effects of overexpression of Nogo-B on cell motility could be partially abolished by RNA interference against Fibulin-5. These results suggest that Nogo-B functions as an inducer of cervical cancer metastasis and that this effect is mediated, at least in part, through Fibulin-5.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Blotting, Western
  • Cell Adhesion*
  • Cell Movement*
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition*
  • Extracellular Matrix Proteins / antagonists & inhibitors
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism*
  • Female
  • Humans
  • Myelin Proteins / genetics
  • Myelin Proteins / metabolism*
  • Nogo Proteins
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured
  • Uterine Cervical Neoplasms / mortality
  • Uterine Cervical Neoplasms / pathology*
  • Uterine Cervical Neoplasms / therapy

Substances

  • Extracellular Matrix Proteins
  • FBLN5 protein, human
  • Myelin Proteins
  • Nogo Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • RTN4 protein, human