Memory of stochastic single-cell apoptotic signaling promotes chemoresistance in neuroblastoma.

Autor:	Hastings JF; Cancer Ecosystems Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia., Latham SL; Cancer Ecosystems Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.; School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Sydney, NSW, Australia., Kamili A; School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Sydney, NSW, Australia.; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia., Wheatley MS; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia., Han JZR; Cancer Ecosystems Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia., Wong-Erasmus M; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia., Phimmachanh M; Cancer Ecosystems Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia., Nobis M; Cancer Ecosystems Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.; School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Sydney, NSW, Australia., Pantarelli C; Cancer Ecosystems Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia., Cadell AL; Cancer Ecosystems Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia., O'Donnell YEI; Cancer Ecosystems Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia., Leong KH; Cancer Ecosystems Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia., Lynn S; Cancer Ecosystems Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia., Geng FS; Cancer Ecosystems Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia., Cui L; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia., Yan S; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia., Achinger-Kawecka J; Cancer Ecosystems Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.; School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Sydney, NSW, Australia., Stirzaker C; Cancer Ecosystems Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.; School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Sydney, NSW, Australia., Norris MD; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.; University of New South Wales Centre for Childhood Cancer Research, UNSW Sydney, Sydney, NSW, Australia., Haber M; School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Sydney, NSW, Australia.; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia., Trahair TN; School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Sydney, NSW, Australia.; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.; Kids Cancer Centre, Sydney Children's Hospital, Randwick, NSW 2031, Australia., Speleman F; Center for Medical Genetics, Ghent University, Ghent, Belgium.; Cancer Research Institute Ghent, Ghent University, Ghent, Belgium., De Preter K; Center for Medical Genetics, Ghent University, Ghent, Belgium.; Cancer Research Institute Ghent, Ghent University, Ghent, Belgium., Cowley MJ; School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Sydney, NSW, Australia.; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.; University of New South Wales Centre for Childhood Cancer Research, UNSW Sydney, Sydney, NSW, Australia., Bogdanovic O; Cancer Ecosystems Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.; School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Sydney, NSW, Australia., Timpson P; Cancer Ecosystems Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.; School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Sydney, NSW, Australia., Cox TR; Cancer Ecosystems Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.; School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Sydney, NSW, Australia., Kolch W; Systems Biology Ireland, School of Medicine, University College Dublin, Belfield, Dublin 4, Ireland.; Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland., Fletcher JI; School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Sydney, NSW, Australia.; Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, NSW, Australia.; University of New South Wales Centre for Childhood Cancer Research, UNSW Sydney, Sydney, NSW, Australia., Fey D; Systems Biology Ireland, School of Medicine, University College Dublin, Belfield, Dublin 4, Ireland., Croucher DR; Cancer Ecosystems Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.; School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Sydney, NSW, Australia.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2023 Mar 03; Vol. 9 (9), pp. eabp8314. Date of Electronic Publication: 2023 Mar 03.
DOI:	10.1126/sciadv.abp8314
Abstrakt:	Gene expression noise is known to promote stochastic drug resistance through the elevated expression of individual genes in rare cancer cells. However, we now demonstrate that chemoresistant neuroblastoma cells emerge at a much higher frequency when the influence of noise is integrated across multiple components of an apoptotic signaling network. Using a JNK activity biosensor with longitudinal high-content and in vivo intravital imaging, we identify a population of stochastic, JNK-impaired, chemoresistant cells that exist because of noise within this signaling network. Furthermore, we reveal that the memory of this initially random state is retained following chemotherapy treatment across a series of in vitro, in vivo, and patient models. Using matched PDX models established at diagnosis and relapse from individual patients, we show that HDAC inhibitor priming cannot erase the memory of this resistant state within relapsed neuroblastomas but improves response in the first-line setting by restoring drug-induced JNK activity within the chemoresistant population of treatment-naïve tumors.
Databáze:	MEDLINE
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