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Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas

Author

Listed:
  • Wen Xue

    (Cold Spring Harbor Laboratory)

  • Lars Zender

    (Cold Spring Harbor Laboratory)

  • Cornelius Miething

    (Cold Spring Harbor Laboratory)

  • Ross A. Dickins

    (Cold Spring Harbor Laboratory
    Howard Hughes Medical Institute)

  • Eva Hernando

    (Memorial Sloan-Kettering Cancer Center)

  • Valery Krizhanovsky

    (Cold Spring Harbor Laboratory)

  • Carlos Cordon-Cardo

    (Memorial Sloan-Kettering Cancer Center)

  • Scott W. Lowe

    (Cold Spring Harbor Laboratory
    Howard Hughes Medical Institute)

Abstract

p53 and tumour regression The p53 tumour suppressor is either mutated or inactivated by other alterations in most human cancers. Two papers in this issue show that even brief reactivation of the endogenous p53 genes in established tumours can cause cancer regression in some animal models. In some tumours, p53 reactivation causes cellular senescence associated with an innate immune response that contributes to tumour clearance. These experiments used gene manipulation to alter p53 levels, but they lend further support to the idea that p53-boosting drugs could be a useful form of cancer treatment.

Suggested Citation

  • Wen Xue & Lars Zender & Cornelius Miething & Ross A. Dickins & Eva Hernando & Valery Krizhanovsky & Carlos Cordon-Cardo & Scott W. Lowe, 2007. "Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas," Nature, Nature, vol. 445(7128), pages 656-660, February.
    • Handle: RePEc:nat:nature:v:445:y:2007:i:7128:d:10.1038_nature05529
    DOI: 10.1038/nature05529
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    Cited by:

    1. Christel F. A. Ramirez & Daniel Taranto & Masami Ando-Kuri & Marnix H. P. Groot & Efi Tsouri & Zhijie Huang & Daniel Groot & Roelof J. C. Kluin & Daan J. Kloosterman & Joanne Verheij & Jing Xu & Seren, 2024. "Cancer cell genetics shaping of the tumor microenvironment reveals myeloid cell-centric exploitable vulnerabilities in hepatocellular carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
    2. Jonuelle Acosta & Qinglan Li & Nelson F. Freeburg & Nivitha Murali & Alexandra Indeglia & Grant P. Grothusen & Michelle Cicchini & Hung Mai & Amy C. Gladstein & Keren M. Adler & Katherine R. Doerig & , 2023. "p53 restoration in small cell lung cancer identifies a latent cyclophilin-dependent necrosis mechanism," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Nanase Igarashi & Kenichi Miyata & Tze Mun Loo & Masatomo Chiba & Aki Hanyu & Mika Nishio & Hiroko Kawasaki & Hao Zheng & Shinya Toyokuni & Shunsuke Kon & Keiji Moriyama & Yasuyuki Fujita & Akiko Taka, 2022. "Hepatocyte growth factor derived from senescent cells attenuates cell competition-induced apical elimination of oncogenic cells," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    4. Samuel A Danziger & Roberta Baronio & Lydia Ho & Linda Hall & Kirsty Salmon & G Wesley Hatfield & Peter Kaiser & Richard H Lathrop, 2009. "Predicting Positive p53 Cancer Rescue Regions Using Most Informative Positive (MIP) Active Learning," PLOS Computational Biology, Public Library of Science, vol. 5(9), pages 1-12, September.
    5. Lingzhi Li & Ting Xiang & Jingjing Guo & Fan Guo & Yiting Wu & Han Feng & Jing Liu & Sibei Tao & Ping Fu & Liang Ma, 2024. "Inhibition of ACSS2-mediated histone crotonylation alleviates kidney fibrosis via IL-1β-dependent macrophage activation and tubular cell senescence," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    6. Yukinari Haraoka & Yuki Akieda & Yuri Nagai & Chihiro Mogi & Tohru Ishitani, 2022. "Zebrafish imaging reveals TP53 mutation switching oncogene-induced senescence from suppressor to driver in primary tumorigenesis," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    7. Rana Salam & Alexa Saliou & Franck Bielle & Mathilde Bertrand & Christophe Antoniewski & Catherine Carpentier & Agusti Alentorn & Laurent Capelle & Marc Sanson & Emmanuelle Huillard & Léa Bellenger & , 2023. "Cellular senescence in malignant cells promotes tumor progression in mouse and patient Glioblastoma," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    8. Yuling Xiao & Jiang Chen & Hui Zhou & Xiaodong Zeng & Zhiping Ruan & Zhangya Pu & Xingya Jiang & Aya Matsui & Lingling Zhu & Zohreh Amoozgar & Dean Shuailin Chen & Xiangfei Han & Dan G. Duda & Jinjun , 2022. "Combining p53 mRNA nanotherapy with immune checkpoint blockade reprograms the immune microenvironment for effective cancer therapy," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    9. Jean-Philippe Coppé & Christopher K Patil & Francis Rodier & Yu Sun & Denise P Muñoz & Joshua Goldstein & Peter S Nelson & Pierre-Yves Desprez & Judith Campisi, 2008. "Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor," PLOS Biology, Public Library of Science, vol. 6(12), pages 1-1, December.
    10. Subha Philip & Muhammad Atif Zahoor & Huijun Zhi & Yik-Khuan Ho & Chou-Zen Giam, 2014. "Regulation of Human T-Lymphotropic Virus Type I Latency and Reactivation by HBZ and Rex," PLOS Pathogens, Public Library of Science, vol. 10(4), pages 1-12, April.
    11. Benjamin Assouline & Rachel Kahn & Lutfi Hodali & Reba Condiotti & Yarden Engel & Ela Elyada & Tzlil Mordechai-Heyn & Jason R. Pitarresi & Dikla Atias & Eliana Steinberg & Tirza Bidany-Mizrahi & Esthe, 2024. "Senescent cancer-associated fibroblasts in pancreatic adenocarcinoma restrict CD8+ T cell activation and limit responsiveness to immunotherapy in mice," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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