Penfluridol represses integrin expression in breast cancer through induction of reactive oxygen species and downregulation of Sp transcription factors

Erik Hedrick, Xi Li, Stephen Safe

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

It was recently demonstrated the penfluridol inhibited breast tumor growth and metastasis and this was associated with downregulation of α6- and β4-integrins. In this study, we observed the penfluridol induced reactive oxygen species (ROS) and this was the primary mechanism of action. Penfluridol-mediated growth inhibition, induction of apoptosis, and inhibition of breast cancer cell migration was attenuated after cotreatment with glutathione. Penfluridol also downregulated Sp transcription factors Sp1, Sp3, and Sp4 through epigenetic downregulation of cMyc and cMyc-regulated miRNAs (miR27a and miR20a/miR17) and induction of the miR-regulated Sp transcriptional repressors ZBTB10 and ZBTB4. α6- and β4-integrins as well as α5- and β1-integrins are Sp-regulated genes that are also coregulated by the orphan nuclear receptor NR4A1 and these integrins can be targeted by agents such as penfluridol that suppress Sp1, Sp3, and Sp4 and also by NR4A1 antagonists.

Original languageEnglish (US)
Pages (from-to)205-216
Number of pages12
JournalMolecular Cancer Therapeutics
Volume16
Issue number1
DOIs
StatePublished - Jan 2017
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Penfluridol represses integrin expression in breast cancer through induction of reactive oxygen species and downregulation of Sp transcription factors'. Together they form a unique fingerprint.

Cite this