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

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 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.DOI: http://dx.doi.org/10.7554/eLife.12203.001

RHO binding to FAM65A regulates Golgi reorientation during cell migration

“…3B), collectively suggesting that MST4 and, to a lesser extent, MST3, but not YSK1, constitute all endogenous GCKIII kinase activity. Neither serum stimulation, which activates RHO proteins, as indicated by an increase in myosin light chain (MLC, specifically MYL9, MYL12A and MYL12B) phosphorylation (Kümper et al, 2016), nor TAT-C3 treatment, which inactivates them (Sahai and Olson, 2006), affected GCKIII activity (Fig. 3A,B).…”

The ROCKs on which tumour cells thrive

“…Once activated, Rho GTPases bind to and activate a network of other proteins in cells, including the enzymes ROCK1 and ROCK2 (Rho-associated, coiled-coil-containing protein kinases; Riento and Ridley, 2003). Now, in eLife, Sandra Kümper of the Institute of Cancer Research (ICR) and colleagues – including the late Christopher Marshall – report that ROCK activity is essential for tumours to form in mice (Kümper et al, 2016). …”

Rutin Prevents High Glucose-Induced Renal Glomerular Endothelial Hyperpermeability by Inhibiting the ROS/Rhoa/ROCK Signaling Pathway

“…Rho kinase (ROCK) is one of the first downstream targets of RhoA. RhoA/ROCK signaling regulates cell functions, including contraction [10], migration [11], adhesion [12], and cell cycle progression [13]. RhoA/ROCK signaling has recently attracted extensive attention as an important contributor to diabetic renal disease [14].…”