ZNF750 represses breast cancer invasion via epigenetic control of prometastatic genes

Matteo Cassandri, Alessio Butera, Ivano Amelio, Anna Maria Lena, Manuela Montanaro, Alessandro Mauriello, Lucia Anemona, Eleonora Candi, Richard A. Knight, Massimiliano Agostini, Gerry Melino

Research output: Contribution to journalArticlepeer-review

Abstract

Breast cancer is the second leading cause of cancer-related deaths among women, largely due to the progression of a significant fraction of primary tumours to the metastatic stage. Here, we show that zinc-finger protein 750 (ZNF750) opposes the migration and invasion of breast cancer cells by repressing a prometastatic transcriptional programme, which includes genes involved in focal adhesion and extracellular matrix interactions, such as LAMB3 and CTNNAL1. Mechanistically, ZNF750 recruits the epigenetic modifiers KDM1A and HDAC1 to the promoter regions of LAMB3 and CTNNAL1, influencing histone marks and transactivating these genomic sites. Gene expression analysis in cancer patient datasets indicated that ZNF750 and its targets were negative prognostic factors in breast cancer. Together, our findings shed light on the molecular mechanism by which ZNF750 regulates cell migration and invasion, suggesting a role in breast cancer metastasis.

Original languageEnglish
Pages (from-to)4331-4343
Number of pages13
JournalOncogene
Volume39
Issue number22
DOIs
Publication statusPublished - May 28 2020

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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