Cutty, SJ;
Hughes, FA;
Ortega-Prieto, P;
Desai, S;
Thomas, P;
Fets, LV;
Secrier, M;
(2024)
Pro-survival roles for p21(Cip1/Waf1) in non-small cell lung cancer.
British Journal of Cancer
10.1038/s41416-024-02928-9.
(In press).
Preview |
Text
Secrier_s41416-024-02928-9.pdf Download (2MB) | Preview |
Abstract
Background: Quiescence is reversible proliferative arrest. Multiple mechanisms regulate quiescence that are not fully understood. High expression of the CDK inhibitor p21Cip1/Waf1 correlates with a poor prognosis in non-small cell lung cancer (NSCLC) and, in non-transformed cells, p21 promotes quiescence after replication stress. We tested whether NSCLC cells enter p21-dependent quiescence and if this is advantageous to NSCLC cells. // Methods: Through analysis of patient data and quantitative, single-cell, timelapse imaging of genetically-engineered NSCLC reporter cell lines we investigated the role of p21 in NSCLC during normal proliferation and after chemotherapy. // Results: High p21 expression correlates with a poor prognosis in TP53 wild-type, but not TP53 mutant, NSCLC patients and TP53 wild-type NSCLC cells can enter p21-dependent quiescence, downstream of replication stress. Without p21, unrepaired DNA damage propagates into S-phase and cells display increased genomic instability. p21 expression confers survival advantages to TP53 wild-type NSCLC cells, during proliferation and after chemotherapy. p21 can promote tumour relapse by allowing recovery from both G1 and G2 arrests after chemotherapy. // Conclusions: p21-dependent quiescence exists in TP53 wild-type NSCLC cells and provides survival advantages to these cells. Targeting p21 function in TP53 wild-type tumours could lead to better outcomes for chemotherapy treatment in NSCLC patients.
| Type: | Article |
|---|---|
| Title: | Pro-survival roles for p21(Cip1/Waf1) in non-small cell lung cancer |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41416-024-02928-9 |
| Publisher version: | https://doi.org/10.1038/s41416-024-02928-9 |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10202746 |
Archive Staff Only
 |
View Item |
