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

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...

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Bibliographic Details
Published in:eLife 2016-01, Vol.5, p.e12994
Main Authors: Kümper, Sandra, Mardakheh, Faraz K, McCarthy, Afshan, Yeo, Maggie, Stamp, Gordon W, Paul, Angela, Worboys, Jonathan, Sadok, Amine, Jørgensen, Claus, Guichard, Sabrina, Marshall, Christopher J
Format: Article
Language:English
Subjects:
Actin
actin cytoskeleton
Actomyosin
actomyosin contractility
Adenoviruses
Animal models
Animals
Cancer
Cancer Biology
Carcinogenesis
Carcinoma, Non-Small-Cell Lung - pathology
Cell adhesion & migration
Cell Biology
Cell culture
Cell cycle
Cell growth
Cell Proliferation
cellular senescence
Contractility
Cytoskeleton
Defects
Embryos
Fibroblasts
Gene Knockout Techniques
Guanine nucleotide-binding protein
Guanosine triphosphatases
Health aspects
Isoforms
Kinases
Medical research
Melanoma
Melanoma - pathology
Mice
Non-small cell lung carcinoma
Observations
Peptides
Phosphatase
Phosphorylation
Phosphotransferases
Proteins
Proteomics
rho kinase
Rho-associated kinase
rho-Associated Kinases - genetics
rho-Associated Kinases - metabolism
ROCK
Rodents
Roles
Senescence
Tumorigenesis
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Summary: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 the 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.
ISSN:2050-084X
2050-084X
DOI:10.7554/elife.12203