Zinc finger protein 367 promotes metastasis by inhibiting the Hippo pathway in breast cancer

Oncogene. 2020 Mar;39(12):2568-2582. doi: 10.1038/s41388-020-1166-y. Epub 2020 Jan 27.

Abstract

Circulating tumor cells (CTC) disseminating is an important cause of distant metastasis. However, the mechanism involved in increasing the numbers of CTCs in breast cancer is unclear. Herein, Zinc finger protein 367 (ZNF367) was identified as a potential prometastatic gene in an integrative breast cancer datasets. ZNF367 was upregulated in breast cancer tissues and cell lines, and significantly correlated with poorer metastasis-free and overall survivals in patients. ZNF367 promoted tumor metastasis accompanied with increase of CTC numbers. Mechanistically, ZNF367 interacted with chromatin remodeling protein BRG1 and transcriptionally activated CIT and TP53BP2, leading to the inhibition of the Hippo pathway and activation of YAP1, which gave rise to the resistance of anoikis and increased CTCs in the blood circulation. More importantly, administration of a YAP1 inhibitor Verteporfin resensitized ZNF367-overexpressing breast cancer cells to anoikis and abrogated metastasis. Our findings addressed the importance of ZNF367 in breast cancer as a prognostic biomarker and offered a potential therapeutic strategy for the treatment of a subset of metastatic breast cancer with ZNF367 overexpression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / antagonists & inhibitors
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Anoikis
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • DNA Helicases / metabolism
  • Female
  • Hippo Signaling Pathway
  • Humans
  • Kruppel-Like Transcription Factors / metabolism*
  • Lung Neoplasms / secondary
  • MAP Kinase Signaling System
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Metastasis*
  • Nuclear Proteins / metabolism
  • Prognosis
  • Protein Serine-Threonine Kinases / metabolism*
  • Survival Rate
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / metabolism
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • Kruppel-Like Transcription Factors
  • Nuclear Proteins
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human
  • ZNF367 protein, human
  • Protein Serine-Threonine Kinases
  • SMARCA4 protein, human
  • DNA Helicases