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

D. Wang, W. Shi, Y. Tang, Y. Liu, K. He, Y. Hu, J. Li, Y. Yang, J. Song

Research output: Contribution to journalArticle

24 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)885-898
Number of pages14
JournalOncogene
Volume36
Issue number7
DOIs
StatePublished - Feb 16 2017

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Wang, D., Shi, W., Tang, Y., Liu, Y., He, K., Hu, Y., Li, J., Yang, Y., & Song, J. (2017). Prefoldin 1 promotes EMT and lung cancer progression by suppressing cyclin A expression. Oncogene, 36(7), 885-898. https://doi.org/10.1038/onc.2016.257