Prefoldin 1 promotes EMT and lung cancer progression by suppressing cyclin A expression

Oncogene. 2017 Feb 16;36(7):885-898. doi: 10.1038/onc.2016.257. Epub 2016 Oct 3.

Abstract

Prefoldin (PFDN) is a co-chaperone protein that is primarily known for its classic cytoplasmic functions in the folding of actin and tubulin monomers during cytoskeletal assembly. Here, we report a marked increase in prefoldin subunit 1 (PFDN1) levels during the transforming growth factor (TGF)-β1-mediated epithelial-mesenchymal transition (EMT) and in human lung tumor tissues. Interestingly, the nuclear localization of PFDN1 was also detected. These observations suggest that PFDN1 may be essential for important novel functions. Overexpression of PFDN1 induced EMT and cell invasion. In sharp contrast, knockdown of PFDN1 generated the opposite effects. Overexpression of PFDN1 was also found to induce lung tumor growth and metastasis. Further experiments showed that PFDN1 overexpression inhibits the expression of cyclin A. PFDN1 suppressed cyclin A expression by directly interacting with the cyclin A promoter at the transcriptional start site. Strikingly, cyclin A overexpression abolished the above PFDN1-mediated effects on the behavior of lung cancer cells, whereas cyclin A knockdown alone induced EMT and increased cell migration and invasion ability. This study reveals that the TGF-β1/PFDN1/cyclin A axis is essential for EMT induction and metastasis of lung cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Cycle
  • Cell Movement
  • Cell Proliferation
  • Cyclin A1 / antagonists & inhibitors*
  • Cyclin A1 / genetics
  • Cyclin A1 / metabolism
  • Disease Progression
  • Epithelial-Mesenchymal Transition*
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / secondary*
  • Mice
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Transforming Growth Factor beta1
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • CCNA1 protein, human
  • Cyclin A1
  • Molecular Chaperones
  • Transforming Growth Factor beta1
  • prefoldin