4.1N suppresses hypoxia-induced epithelial-mesenchymal transition in epithelial ovarian cancer cells

Mol Med Rep. 2016 Jan;13(1):837-44. doi: 10.3892/mmr.2015.4634. Epub 2015 Dec 1.

Abstract

Protein 4.1N (4.1N) is a member of the protein 4.1 family and is essential for the regulation of cell adhesion, motility and signaling. Previous studies have suggested that 4.1N may serve a tumor suppressor role. However, the molecular mechanisms remain unclear. In the current study, the role of 4.1N in the downregulation of hypoxia‑induced factor 1α (HIF‑1α) under hypoxic conditions and therefore the suppression of hypoxia induced epithelial‑mesenchymal transition (EMT) was investigated. The data were obtained from overexpressed and knockdown 4.1N epithelial ovarian cancer (EOC) cell lines. It was identified that 4.1N was capable of regulating the sub‑cellular localization and expression levels of HIF‑1α, by which 4.1N served a dominant role in the suppression of hypoxia‑induced EMT and associated genes. Collectively, the data of the current study identified 4.1N as an inhibitor of hypoxia‑induced tumor progression in EOC cells and highlighted its potential role in EOC therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cadherins / metabolism
  • Carcinoma, Ovarian Epithelial
  • Cell Hypoxia
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Cell Survival
  • Cytoskeletal Proteins / metabolism*
  • Epithelial-Mesenchymal Transition*
  • Female
  • Gene Knockdown Techniques
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Membrane Proteins / metabolism*
  • Models, Biological
  • Neoplasms, Glandular and Epithelial / metabolism*
  • Neoplasms, Glandular and Epithelial / pathology*
  • Neuropeptides / metabolism*
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology*

Substances

  • Cadherins
  • Cytoskeletal Proteins
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Membrane Proteins
  • Neuropeptides
  • erythrocyte membrane protein band 4.1-like 1