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Rho-associated kinase (ROCK) function is essential for cell cycle progression, senescence and tumorigenesis

Sandra Kümper1, Faraz K Mardakheh1, Afshan McCarthy1

  • 1Division of Cancer Biology, Institute of Cancer Research, London, United Kingdom.

Elife
|January 15, 2016
PubMed

Insights

Rho-associated kinases (ROCK1/2) maintain cell proliferation and actomyosin contractility. Their combined loss halts cell-cycle progression and blocks tumor formation in cancer models.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Rho-associated kinases (ROCK1/2) are key regulators of the actin cytoskeleton.
  • Their specific roles in cell proliferation and cancer development remain largely uncharacterized.

Purpose of the Study:

  • To investigate the function of ROCK1 and ROCK2 in cell proliferation and tumorigenesis.
  • To elucidate the molecular mechanisms underlying ROCK's role in cancer initiation and progression.

Main Methods:

  • Utilized mouse models of non-small cell lung cancer and melanoma.
  • Performed genetic deletion of Rock1 and Rock2, individually and concurrently.
  • Analyzed cell-cycle progression, cellular senescence, and expression of key cell-cycle proteins (CyclinA, CKS1, CDK1).

Main Results:

  • ROCK1 and ROCK2 act redundantly to maintain actomyosin contractility and support cell proliferation.
  • Loss of both ROCK1 and ROCK2 induces cell-cycle arrest and cellular senescence.
  • Down-regulation of CyclinA, CKS1, and CDK1 was observed upon ROCK loss.
  • Simultaneous genetic deletion of Rock1 and Rock2 completely inhibited tumor formation in cancer models.

Conclusions:

  • ROCK1 and ROCK2 play indispensable, yet redundant, roles in cell cycle progression and tumorigenesis.
  • ROCK's function in proliferation and cancer may be mediated through the maintenance of cellular contractility.
  • Targeting ROCK isoforms could represent a therapeutic strategy for cancer treatment.
Keywords:
ROCKactin cytoskeletonactomyosin contractilitycancer biologycell biologycell proliferationcellular senescencemouserho kinase

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