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p21（Cip1/Waf1）在非小细胞肺癌中的促生存作用。

Pro-survival roles for p21(Cip1/Waf1) in non-small cell lung cancer.

作者信息

Cutty S J, Hughes F A, Ortega-Prieto P, Desai S, Thomas P, Fets L V, Secrier M, Barr A R

机构信息

Institute of Clinical Sciences, Imperial College London, London, UK.

Department of Mathematics, Imperial College London, London, UK.

出版信息

Br J Cancer. 2025 Mar;132(5):421-437. doi: 10.1038/s41416-024-02928-9. Epub 2024 Dec 20.

DOI:10.1038/s41416-024-02928-9
PMID:39706988
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11876327/
Abstract

BACKGROUND

Quiescence is reversible proliferative arrest. Multiple mechanisms regulate quiescence that are not fully understood. High expression of the CDK inhibitor p21 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.

摘要

背景

静止是一种可逆的增殖停滞。多种机制调节静止，但尚未完全了解。细胞周期蛋白依赖性激酶（CDK）抑制剂p21的高表达与非小细胞肺癌（NSCLC）的不良预后相关，并且在未转化细胞中，p21在复制应激后促进静止。我们测试了NSCLC细胞是否进入p21依赖性静止状态，以及这对NSCLC细胞是否有利。

方法

通过分析患者数据以及对基因工程NSCLC报告细胞系进行定量、单细胞、延时成像，我们研究了p21在正常增殖和化疗后NSCLC中的作用。

结果

在TP53野生型而非TP53突变型NSCLC患者中，p21高表达与不良预后相关，并且TP53野生型NSCLC细胞在复制应激下游可进入p21依赖性静止状态。没有p21时，未修复的DNA损伤会传播到S期，细胞显示出基因组不稳定性增加。p21表达在增殖期间和化疗后赋予TP53野生型NSCLC细胞生存优势。p21可通过使化疗后从G1期和G2期停滞中恢复来促进肿瘤复发。

结论

TP53野生型NSCLC细胞中存在p21依赖性静止状态，并为这些细胞提供生存优势。靶向TP53野生型肿瘤中的p21功能可能会使NSCLC患者的化疗治疗获得更好的结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0aaa/11876327/0a68b3903034/41416_2024_2928_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0aaa/11876327/dc770585113d/41416_2024_2928_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0aaa/11876327/a994e71f9128/41416_2024_2928_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0aaa/11876327/4b5be1c4a9f3/41416_2024_2928_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0aaa/11876327/3674ac94fafd/41416_2024_2928_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0aaa/11876327/1c6544e21c50/41416_2024_2928_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0aaa/11876327/0a68b3903034/41416_2024_2928_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0aaa/11876327/dc770585113d/41416_2024_2928_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0aaa/11876327/a994e71f9128/41416_2024_2928_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0aaa/11876327/4b5be1c4a9f3/41416_2024_2928_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0aaa/11876327/3674ac94fafd/41416_2024_2928_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0aaa/11876327/1c6544e21c50/41416_2024_2928_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0aaa/11876327/0a68b3903034/41416_2024_2928_Fig6_HTML.jpg

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Mol Cell. 2023 Nov 16;83(22):4062-4077.e5. doi: 10.1016/j.molcel.2023.10.016.
2
A cell cycle centric view of tumour dormancy.以细胞周期为中心的肿瘤休眠观点。
Br J Cancer. 2023 Nov;129(10):1535-1545. doi: 10.1038/s41416-023-02401-z. Epub 2023 Aug 22.
3
The intensities of canonical senescence biomarkers integrate the duration of cell-cycle withdrawal.典型衰老生物标志物的强度整合了细胞周期退出的持续时间。
Nat Commun. 2023 Jul 27;14(1):4527. doi: 10.1038/s41467-023-40132-0.
4
Loss of CDK4/6 activity in S/G2 phase leads to cell cycle reversal.CDK4/6 活性丧失导致 S/G2 期细胞周期逆转。
Nature. 2023 Jul;619(7969):363-370. doi: 10.1038/s41586-023-06274-3. Epub 2023 Jul 5.
5
Cyclin E-induced replicative stress drives p53-dependent whole-genome duplication.细胞周期蛋白E诱导的复制应激驱动p53依赖的全基因组复制。
Cell. 2023 Feb 2;186(3):528-542.e14. doi: 10.1016/j.cell.2022.12.036. Epub 2023 Jan 20.
6
The molecular architecture of cell cycle arrest.细胞周期阻滞的分子结构。
Mol Syst Biol. 2022 Sep;18(9):e11087. doi: 10.15252/msb.202211087.
7
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Nat Commun. 2022 Aug 15;13(1):4767. doi: 10.1038/s41467-022-32448-0.
8
Latency reversal plus natural killer cells diminish HIV reservoir in vivo.潜伏期逆转加自然杀伤细胞减少体内 HIV 储存库。
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10
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