ArticleMolecular biology of the cell2002
Post-transcriptional down-regulation of ROCKI/Rho-kinase through an MEK-dependent pathway leads to cytoskeleton disruption in Ras-transformed fibroblasts.
Article in Molecular biology of the cell, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 81 citations in OpenAlex.
- Multi-OMICs landscape of SARS-CoV-2-induced host responses in human lung epithelial cells.iScience · 2023Article
- Emerging evidence on Monkeypox: resurgence, global burden, molecular insights, genomics and possible management.Frontiers in cellular and infection microbiology · 2023Review
- Regulation of smooth muscle contraction by monomeric non-RhoA GTPases.British journal of pharmacology · 2020Review
- Oncogenic Signaling Alters Cell Shape and Mechanics to Facilitate Cell Division under Confinement.Developmental cell · 2020Article
- Differential KrasConvergent science physical oncology · 2016Article
- ERK1/2 and AKT are vital factors in regulation of the migration of rat Schwann cells.The Journal of veterinary medical science · 2015Article
- Article
- Inhibitory mechanism of FAT4 gene expression in response to actin dynamics during Src-induced carcinogenesis.PloS one · 2015Article
- ROCK1 is a potential combinatorial drug target for BRAF mutant melanoma.Molecular systems biology · 2014Article
- The Ras-ERK pathway modulates cytoskeleton organization, cell motility and lung metastasis signature genes in MDA-MB-231 LM2.Oncogene · 2014Article
- Crosstalk of Ras and Rho: activation of RhoA abates Kras-induced liver tumorigenesis in transgenic zebrafish models.Oncogene · 2014Article
- Activin B antagonizes RhoA signaling to stimulate mesenchymal morphology and invasiveness of clear cell renal cell carcinomas.PloS one · 2014Article
- Inhibition of platelet-derived growth factor receptor signaling regulates Oct4 and Nanog expression, cell shape, and mesenchymal stem cell potency.Stem cells (Dayton, Ohio) · 2012Article
- Cutaneous human papillomavirus type 38 E7 regulates actin cytoskeleton structure for increasing cell proliferation through CK2 and the eukaryotic elongation factor 1A.Journal of virology · 2011Article
- A case of variant angina in a patient under chronic treatment with sorafenib.Nature reviews. Clinical oncology · 2010Article
- Gene expression profiling of monkeypox virus-infected cells reveals novel interfaces for host-virus interactions.Virology journal · 2010Article
- From autoinhibition to inhibition in trans: the Raf-1 regulatory domain inhibits Rok-alpha kinase activity.The Journal of cell biology · 2009Article
- Sorafenib targets dysregulated Rho kinase expression and portal hypertension in rats with secondary biliary cirrhosis.British journal of pharmacology · 2009Article
- An essential role for p120-catenin in Src- and Rac1-mediated anchorage-independent cell growth.The Journal of cell biology · 2009Article
- S1P differentially regulates migration of human ovarian cancer and human ovarian surface epithelial cells.Molecular cancer therapeutics · 2008Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Transformation by oncogenic Ras profoundly alters actin cytoskeleton organization. We investigated Ras-dependent signaling pathways involved in cytoskeleton disruption by transfecting normal rat kidney (NRK) cells with different Ras mutants. RasV12S35, a mutant known to activate specifically the Raf/MAPK pathway, led to stress fiber and focal contact disruption, whereas the adherens junctions remained intact. Next, we found that pharmacological inhibition of MEK was sufficient to restore the cytoskeletal defects of ras-transformed NRK cells, including assembly of stress fibers and focal contacts, but it did not induce reorganization of the cell-cell junctions. Investigating the mechanism underlying this phenotypic reversion, we found that the sustained MAPK signaling resulting from Ras-transformation down-regulated the expression of ROCKI and Rho-kinase, two-Rho effectors required for stress fiber formation, at the post-transcriptional level. On MEK inhibition, ROCKI/Rho-kinase expression and cofilin phosphorylation were increased, demonstrating that the Rho-kinase/LIM-kinase/cofilin pathway was functionally restored. Finally, using dominant negative or constitutively active mutants, we demonstrated that expression of ROCKI/Rho-kinase was both necessary and sufficient to promote cytoskeleton reorganization in NRK/ras cells. These findings further establish the Ras/MAPK pathway as the critical pathway involved in cytoskeleton disruption during Ras-transformation, and they suggest a new mechanism, involving alteration in ROCKI/Rho-kinase expression, by which oncogenic Ras can specifically target the actin-based cytoskeleton and achieve morphological transformation of the cells.
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