TY - JOUR
T1 - ZNF750 represses breast cancer invasion via epigenetic control of prometastatic genes
AU - Cassandri, Matteo
AU - Butera, Alessio
AU - Amelio, Ivano
AU - Lena, Anna Maria
AU - Montanaro, Manuela
AU - Mauriello, Alessandro
AU - Anemona, Lucia
AU - Candi, Eleonora
AU - Knight, Richard A.
AU - Agostini, Massimiliano
AU - Melino, Gerry
N1 - Funding Information:
Acknowledgements We would like to thank Dr Annalisa Conti for helpful comments and suggestions and K. Dudek and C. Jones for assistance in gene microarray analysis. This work has been supported by the Medical Research Council (to GM) UK, the Associazione Italiana per la Ricerca contro il Cancro (AIRC) (to GM; IG#20473 (2018–2022)), the AIRC (to EC; IG#22206 (2019–2023)), the AIRC (Start-Up to IA; ID 23219), the Ministero Salute, IDI-IRCCS (RC to EC), and the Italian Ministry of Foreign Affairs and International Cooperation (to EC). The work has also been supported by Regione Lazio through the LazioInnova Progetto Gruppo di Ricerca n 85-2017-14986 (to GM).
Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/5/28
Y1 - 2020/5/28
N2 - 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.
AB - 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.
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U2 - 10.1038/s41388-020-1277-5
DO - 10.1038/s41388-020-1277-5
M3 - Article
C2 - 32313225
AN - SCOPUS:85083706898
VL - 39
SP - 4331
EP - 4343
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 22
ER -