1. Cancer Biology
  2. Cell Biology
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Rho-associated kinase (ROCK) function is essential for cell cycle progression, senescence and tumorigenesis

  1. Sandra Kümper  Is a corresponding author
  2. Faraz K Mardakheh
  3. Afshan McCarthy
  4. Maggie Yeo
  5. Gordon W Stamp
  6. Angela Paul
  7. Jonathan Worboys
  8. Amine Sadok
  9. Claus Jørgensen
  10. Sabrina Guichard
  11. Christopher J Marshall
  1. Institute of Cancer Research, United Kingdom
  2. Cancer Research UK London Research Institute, United Kingdom
  3. Cancer Research UK Manchester Institute, United Kingdom
Research Article
  • Cited 68
  • Views 6,425
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Cite this article as: eLife 2016;5:e12203 doi: 10.7554/eLife.12203

Abstract

Rho-associated kinases 1 and 2 (ROCK1/2) are Rho-GTPase effectors that control key aspects of the actin cytoskeleton, but their role in proliferation and cancer initiation or progression is not known. Here we provide evidence that ROCK1 and ROCK2 act redundantly to maintain actomyosin contractility and cell proliferation and that their loss leads to cell-cycle arrest and cellular senescence. This phenotype arises from down-regulation of the essential cell-cycle proteins CyclinA, CKS1 and CDK1. Accordingly, while loss of either Rock1 or Rock2 had no negative impact on tumorigenesis in mouse models of non-small cell lung cancer and melanoma, loss of both blocked tumor formation, as no tumors arise in which both Rock1 and Rock2 have been genetically deleted. Our results reveal an indispensable role for ROCK, yet redundant role for isoforms 1 and 2, in cell cycle progression and tumorigenesis, possibly through the maintenance of cellular contractility.

Article and author information

Author details

  1. Sandra Kümper

    Division of Cancer Biology, Institute of Cancer Research, London, United Kingdom
    For correspondence
    sandra.kuemper@icr.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
  2. Faraz K Mardakheh

    Division of Cancer Biology, Institute of Cancer Research, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Afshan McCarthy

    Division of Cancer Biology, Institute of Cancer Research, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Maggie Yeo

    Division of Cancer Biology, Institute of Cancer Research, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Gordon W Stamp

    Experimental Pathology Laboratory, Cancer Research UK London Research Institute, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Angela Paul

    Division of Cancer Biology, Institute of Cancer Research, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  7. Jonathan Worboys

    Cancer Research UK Manchester Institute, Manchester, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Amine Sadok

    Division of Cancer Biology, Institute of Cancer Research, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  9. Claus Jørgensen

    Cancer Research UK Manchester Institute, Manchester, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  10. Sabrina Guichard

    Division of Cancer Biology, Institute of Cancer Research, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  11. Christopher J Marshall

    Division of Cancer Biology, Institute of Cancer Research, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: All animal procedures were approved by the Animal Ethics Committee of the Institute of Cancer Research in accordance with National Home Office regulations under the Animals (Scientific Procedures) Act 1986. The date of approval of the current project license under which this work was carried out was the 07/09/13.

Reviewing Editor

  1. Roger Davis, Howard Hughes Medical Institute & University of Massachusetts Medical School, United States

Publication history

  1. Received: October 9, 2015
  2. Accepted: January 13, 2016
  3. Accepted Manuscript published: January 14, 2016 (version 1)
  4. Version of Record published: March 7, 2016 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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  1. Further reading

Further reading

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