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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

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


Authors

Norazalina Saad

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RAMIRO ALBERIO ramiro.alberio@nottingham.ac.uk
Professor of Developmental Biology

ANDREW JOHNSON andrew.d.johnson@nottingham.ac.uk
Professor of Cell and Developmental Biology

Richard D. Emes

Tom C. Giles

Philip Clarke

ANNA GRABOWSKA ANNA.GRABOWSKA@NOTTINGHAM.AC.UK
Professor of Cancer Microenvironment



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.

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), 16008-16027. https://doi.org/10.18632/oncotarget.24664

Journal Article Type Article
Acceptance Date Feb 27, 2018
Online Publication Date Mar 23, 2018
Publication Date Mar 23, 2018
Deposit Date Apr 10, 2018
Publicly Available Date Mar 29, 2024
Journal Oncotarget
Electronic ISSN 1949-2553
Publisher Impact Journals
Peer Reviewed Peer Reviewed
Volume 9
Issue 22
Pages 16008-16027
DOI https://doi.org/10.18632/oncotarget.24664
Keywords reprogramming; tumour reversion; dormancy; breast cancer; axolotl oocytes
Public URL https://nottingham-repository.worktribe.com/output/921561
Publisher URL https://www.oncotarget.com/article/24664/text/

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