Zampetidis, Christos P., Galanos, Panagiotis ORCID: 0000-0003-1403-4685, Angelopoulou, Andriani, Zhu, Yajie, Polyzou, Aikaterini, Karamitros, Timokratis ORCID: 0000-0003-0841-9159, Kotsinas, Athanassios, Lagopati, Nefeli, Mourkioti, Ioanna, Mirzazadeh, Reza, Polyzos, Alexandros, Garnerone, Silvano, Mizi, Athanasia, Gusmao, Eduardo G., Sofiadis, Konstantinos, Gal, Zita, Larsen, Dorthe H., Pefani, Dafni-Eleftheria, Demaria, Marco ORCID: 0000-0002-8429-4813, Tsirigos, Aristotelis, Crosetto, Nicola, Maya-Mendoza, Apolinar, Papaspyropoulos, Angelos, Evangelou, Konstantinos, Bartek, Jiri, Papantonis, Argyris and Gorgoulis, Vassilis G. (2021). A recurrent chromosomal inversion suffices for driving escape from oncogene-induced senescence via subTAD reorganization. Mol. Cell, 81 (23). S. 4907 - 4933. CAMBRIDGE: CELL PRESS. ISSN 1097-4164

Full text not available from this repository.

Abstract

Oncogene-induced senescence (OIS) is an inherent and important tumor suppressor mechanism. However, if not removed timely via immune surveillance, senescent cells also have detrimental effects. Although this has mostly been attributed to the senescence-associated secretory phenotype (SASP) of these cells, we recently proposed that escape from the senescent state is another unfavorable outcome. The mechanism underlying this phenomenon remains elusive. Here, we exploit genomic and functional data from a prototypical human epithelial cell model carrying an inducible CDC6 oncogene to identify an early-acquired recurrent chromosomal inversion that harbors a locus encoding the circadian transcription factor BHLHE40. This inversion alone suffices for BHLHE40 activation upon CDC6 induction and driving cell cycle re-entry of senescent cells, and malignant transformation. Ectopic overexpression of BHLHE40 prevented induction of CDC6-triggered senescence. We provide strong evidence in support of replication stress-induced genomic instability being a causative factor underlying escape from oncogene-induced senescence.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Zampetidis, Christos P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Galanos, PanagiotisUNSPECIFIEDorcid.org/0000-0003-1403-4685UNSPECIFIED
Angelopoulou, AndrianiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhu, YajieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Polyzou, AikateriniUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Karamitros, TimokratisUNSPECIFIEDorcid.org/0000-0003-0841-9159UNSPECIFIED
Kotsinas, AthanassiosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lagopati, NefeliUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mourkioti, IoannaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mirzazadeh, RezaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Polyzos, AlexandrosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garnerone, SilvanoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mizi, AthanasiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gusmao, Eduardo G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sofiadis, KonstantinosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gal, ZitaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Larsen, Dorthe H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pefani, Dafni-EleftheriaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Demaria, MarcoUNSPECIFIEDorcid.org/0000-0002-8429-4813UNSPECIFIED
Tsirigos, AristotelisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Crosetto, NicolaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maya-Mendoza, ApolinarUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Papaspyropoulos, AngelosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Evangelou, KonstantinosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bartek, JiriUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Papantonis, ArgyrisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gorgoulis, Vassilis G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-601988
DOI: 10.1016/j.molcel.2021.10.017
Journal or Publication Title: Mol. Cell
Volume: 81
Number: 23
Page Range: S. 4907 - 4933
Date: 2021
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1097-4164
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CELLULAR SENESCENCE; DNA-REPLICATION; READ ALIGNMENT; GENOMIC INSTABILITY; SECRETORY PHENOTYPE; GENE; TRANSCRIPTION; OVEREXPRESSION; CELLS; STEMMultiple languages
Biochemistry & Molecular Biology; Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60198

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item