elife-12203-v2.pdf (3.75 MB)
Rho-associated kinase (ROCK) function is essential for cell cycle progression, senescence and tumorigenesis
journal contributionposted on 2020-08-20, 16:26 authored by S Kümper, FK Mardakheh, A McCarthy, M Yeo, GW Stamp, A Paul, J Worboys, A Sadok, C Jørgensen, S Guichard, CJ Marshall
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 Rockl 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 Rockl 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.