Skip to main content

Research Repository

Advanced Search

Cancer reversion with oocyte extracts is mediated by cell cycle arrest and induction of tumour dormancy

Saad, Norazalina; Alberio, Ramiro; Johnson, Andrew D.; Emes, Richard D.; Giles, Tom C.; Clarke, Philip; Grabowska, Anna M.; Allegrucci, Cinzia

Authors

Norazalina Saad

Ramiro Alberio

Andrew D. Johnson

RICHARD EMES richard.emes@nottingham.ac.uk
Professor of Bioinformatics

Tom C. Giles

Philip Clarke

Anna M. Grabowska

Cinzia Allegrucci cinzia.allegrucci@nottingham.ac.uk



Abstract

Inducing stable control of tumour growth by tumour reversion is an alternative approach to cancer treatment when eradication of the disease cannot be achieved. The process requires re-establishment of normal control mechanisms that are lost in cancer cells so that abnormal proliferation can be halted. Embryonic environments can reset cellular programmes and we previously showed that axolotl oocyte extracts can reprogram breast cancer cells and reverse their tumorigenicity. In this study, we analysed the gene expression profiles of oocyte extract-treated tumour xenografts to show that tumour reprogramming involves cell cycle arrest and acquisition of a quiescent state. Tumour dormancy is associated with increased P27 expression, restoration of RB function and downregulation of mitogen-activated signalling pathways. We also show that the quiescent state is associated with increased levels of H4K20me3 and decreased H4K20me1, an epigenetic profile leading to chromatin compaction. The epigenetic reprogramming induced by oocyte extracts is required for RB hypophosphorylation and induction of P27 expression, both occurring during exposure to the extracts and stably maintained in reprogrammed tumour xenografts. Therefore, this study demonstrates the value of oocyte molecules for inducing tumour reversion and for the development of new chemoquiescence-based therapies.

Journal Article Type Article
Publication Date Mar 23, 2018
Journal Oncotarget
Electronic ISSN 1949-2553
Publisher Impact Journals
Peer Reviewed Peer Reviewed
Volume 9
Issue 22
APA6 Citation Saad, N., Alberio, R., Johnson, A. D., Emes, R. D., Giles, T. C., Clarke, P., …Allegrucci, C. (2018). Cancer reversion with oocyte extracts is mediated by cell cycle arrest and induction of tumour dormancy. Oncotarget, 9(22), doi:10.18632/oncotarget.24664
DOI https://doi.org/10.18632/oncotarget.24664
Keywords reprogramming; tumour reversion; dormancy; breast cancer; axolotl oocytes
Publisher URL http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=24664&path[]=77373
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

Files

24664-344956-5-PB-Oncotarget paper.pdf (8.5 Mb)
PDF

Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0


24664-344969-2-SP.pdf (2.4 Mb)
PDF

Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0


24664-344970-1-SP (1).docx (17 Kb)
Document

Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0


24664-344971-1-SP (1).docx (15 Kb)
Document

Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0







You might also like



Downloadable Citations

;