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

doi:10.1038/s41388-020-1277-5

ZNF750 represses breast cancer invasion via epigenetic control of prometastatic genes

Oncogene. 2020 May;39(22):4331-4343. doi: 10.1038/s41388-020-1277-5. Epub 2020 Apr 20.

Authors

Matteo Cassandri^{1

2}, Alessio Butera¹, Ivano Amelio^{1

3}, Anna Maria Lena¹, Manuela Montanaro¹, Alessandro Mauriello¹, Lucia Anemona¹, Eleonora Candi^{1

4}, Richard A Knight³, Massimiliano Agostini⁵, Gerry Melino^{6

7}

Affiliations

¹ Department of Experimental Medicine, TOR, University of Rome "Tor Vergata", 00133, Rome, Italy.
² Department of Oncohematology, Bambino Gesu' Children's Hospital, 00146, Rome, Italy.
³ Department of Pathology, MRC Toxicology Unit, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK.
⁴ IDI-IRCCS, via Monti di Creta, 106, 00166, Rome, Italy.
⁵ Department of Experimental Medicine, TOR, University of Rome "Tor Vergata", 00133, Rome, Italy. [email protected].
⁶ Department of Experimental Medicine, TOR, University of Rome "Tor Vergata", 00133, Rome, Italy. [email protected].
⁷ Department of Pathology, MRC Toxicology Unit, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK. [email protected].

PMID: 32313225
DOI: 10.1038/s41388-020-1277-5

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Binding Sites
Breast Neoplasms / genetics
Breast Neoplasms / pathology*
Cell Adhesion Molecules / biosynthesis
Cell Adhesion Molecules / genetics
Cell Line, Tumor
Cell Movement / genetics
Cell Polarity
Datasets as Topic
Female
Focal Adhesions / genetics
Gene Expression Regulation, Neoplastic*
Golgi Apparatus / ultrastructure
Histone Code*
Histone Deacetylase 1 / metabolism
Histone Demethylases / metabolism
Humans
Kalinin
Neoplasm Invasiveness / genetics*
Neoplasm Metastasis / genetics*
Neoplasm Proteins / biosynthesis
Neoplasm Proteins / genetics
Neoplasm Proteins / physiology*
Prognosis
Promoter Regions, Genetic / genetics*
Protein Interaction Mapping
Transcription Factors / physiology*
Transcriptional Activation
Tumor Suppressor Proteins
Wnt Signaling Pathway / genetics
alpha Catenin / biosynthesis
alpha Catenin / genetics

Substances

CTNNAL1 protein, human
Cell Adhesion Molecules
Neoplasm Proteins
Transcription Factors
Tumor Suppressor Proteins
ZNF750 protein, human
alpha Catenin
Histone Demethylases
KDM1A protein, human
HDAC1 protein, human
Histone Deacetylase 1