• Publications
  • Influence
The Rho GTPase Effector ROCK Regulates Cyclin A, Cyclin D1, and p27Kip1 Levels by Distinct Mechanisms
Using a conditionally activated ROCK-estrogen receptor fusion protein, it is found that ROCK activation is sufficient to stimulate G1/S cell cycle progression in NIH 3T3 mouse fibroblasts and revealed that ROCK acts via independent pathways to alter the levels of cell cycle regulatory proteins. Expand
Actomyosin-mediated cellular tension drives increased tissue stiffness and β-catenin activation to induce epidermal hyperplasia and tumor growth.
Tumor number, growth, and progression were increased by ROCK activation, while ROCK blockade was inhibitory, implicating actomyosin-mediated cellular tension and consequent collagen deposition as significant tumor promoters. Expand
Actin-myosin–based contraction is responsible for apoptotic nuclear disintegration
It is shown that apoptotic nuclear disintegration requires actin-myosin contractile force and lamin proteolysis, making apoptosis analogous to, but distinct from, mitosis wherenuclear disintegration results from microtubule-based forces and from lamin phosphorylation and depolymerization. Expand
LIM kinases are required for invasive path generation by tumor and tumor-associated stromal cells
Leading cells require LIMK for matrix degradation and invadopodia formation during collective cell migration during collective Cell migration. Expand
Keratinocyte Differentiation Is Regulated by the Rho and ROCK Signaling Pathway
Analysis of ROCK's role in the regulation of epidermal keratinocyte function by using a pharmacological inhibitor and expressing conditionally active or inactive forms of ROCK-II in primary human keratinocytes indicates that ROCK plays a critical role in regulating the balance between proliferation and differentiation in human kerates. Expand
Loss of autophagy causes a synthetic lethal deficiency in DNA repair
  • Emma Y Liu, N. Xu, +12 authors K. Ryan
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences
  • 7 January 2015
It is reported here that inhibition of autophagy causes elevated proteasomal activity leading to enhanced degradation of checkpoint kinase 1 (Chk1), a pivotal factor for the error-free DNA repair process, homologous recombination (HR). Expand
A novel small-molecule MRCK inhibitor blocks cancer cell invasion
BDP5290 is a potent MRCK inhibitor with activity in cells, resulting in reduced MLC phosphorylation, cell motility and tumour cell invasion. Expand
AP-1 Differentially Expressed Proteins Krp1 and Fibronectin Cooperatively Enhance Rho-ROCK-Independent Mesenchymal Invasion by Altering the Function, Localization, and Activity of Nondifferentially
The results support the concept of an AP-1-regulated multigenic invasion program in which proteins encoded by differentially expressed genes direct the function, localization, and activity of proteins that are not differentially expression to enhance the invasiveness of cells. Expand
Conditional ROCK Activation In vivo Induces Tumor Cell Dissemination and Angiogenesis
The results suggest that ROCK inhibitors would be useful antimetastatic and antiangiogenic chemotherapeutic agents in tumors associated with elevated RhoA, RhoC, ROCK I, or ROCK II expression. Expand
p53-mediated transcriptional regulation and activation of the actin cytoskeleton regulatory RhoC to LIMK2 signaling pathway promotes cell survival
It is shown that RhoC and LIM kinase 2 (LIMK2) are direct p53 target genes induced by genotoxic agents, and activation of LIMK2 also has a pro-survival function following DNA damage. Expand