NHERF1 Suppresses Lung Cancer Cell Migration by Regulation of Epithelial-Mesenchymal Transition

Anticancer Res. 2017 Aug;37(8):4405-4414. doi: 10.21873/anticanres.11835.

Abstract

Background/aim: Na(+)/H(+) exchanger regulatory factor 1 (NHERF1) has been reported to interact with many cancer-related proteins and plays an important role in cancer progression. However, little is known about the biological functions of NHERF1 in lung cancer cells. The aim of the current study was to explore whether NHERF1 is involved in transforming growth factor (TGF)-β1-induced epithelial-mesenchymal transition (EMT) in non-small-cell lung cancer cells.

Materials and methods: The expression of NHERF1 and EMT-associated markers including E-cadherin, N-cadherin, snail family transcriptional repressor 1 (SNAI1) and snail family transcriptional repressor 2 (SLUG) were analyzed by reverse transcription polymerase chain reaction (RT-PCR) and western blotting. The migratory properties of cells were assessed using a wound-healing assay.

Results: TGF-β1-induced a pro-migratory response in the A549 lung cancer cell line, that was consistently associated with corresponding changes in the expression levels of EMT-related genes. The expression of NHERF1 significantly decreased in the TGF-β1-induced A549 cells. Overexpression of NHERF1 significantly inhibited the migratory ability of cells and reversed the TGF-β1-induced mesenchymal phenotype of A549 cells.

Conclusion: These data showed an important role of NHERF1 in the EMT of non-small-cell lung cancer cells, as well as migration.

Keywords: EMT; NHERF1; lung cancer; migration.

MeSH terms

  • A549 Cells
  • Biomarkers, Tumor
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Cell Movement / drug effects
  • Down-Regulation / drug effects
  • Epithelial-Mesenchymal Transition / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Phosphoproteins / genetics*
  • Phosphoproteins / metabolism*
  • Sodium-Hydrogen Exchangers / genetics*
  • Sodium-Hydrogen Exchangers / metabolism*
  • Transforming Growth Factor beta / pharmacology

Substances

  • Biomarkers, Tumor
  • Phosphoproteins
  • Sodium-Hydrogen Exchangers
  • Transforming Growth Factor beta
  • sodium-hydrogen exchanger regulatory factor