ArticleMolecular cancer2011
Inhibition of Rho-associated coiled-coil containing protein kinase enhances the activation of epidermal growth factor receptor in pancreatic cancer cells.
Article in Molecular cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 33 citations in OpenAlex.
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- Antimicrobial, Quorum Sensing Inhibition, and Anti-Cancer Activities of Silver Nanoparticles Synthesized from Kenyan Bacterial Endophytes ofInternational journal of molecular sciences · 2025Article
- Whole genome sequencing identifies rare genetic variants in familial pancreatic cancer patients.Annals of human genetics · 2022Article
- Rho-Associated Protein Kinase Inhibitor and Hypoxia Synergistically Enhance the Self-Renewal, Survival Rate, and Proliferation of Human Stem Cells.Stem cells and cloning : advances and applications · 2022Article
- Synergistic Effect of Laminin and Epidermal Growth Factor on Biological and Morphological Properties of Co-Cultured Myoblasts and Fibroblasts.Tissue engineering and regenerative medicine · 2020Article
- Rock inhibition promotes NaScientific reports · 2020Article
- Proteogenomic Characterization Reveals Therapeutic Vulnerabilities in Lung Adenocarcinoma.Cell · 2020Article
- Targeting Rho GTPase Signaling Networks in Cancer.Frontiers in cell and developmental biology · 2020Review
- ROCK inhibitor enhances the growth and migration of BRAF-mutant skin melanoma cells.Cancer science · 2018Article
- Sortilin as a new membrane inhibitor of EGFR trafficking for overcoming resistance to EGFR inhibitors in non-small cell lung cancer.Journal of thoracic disease · 2018Article
- Y-27632 Increases Sensitivity of PANC-1 Cells to EGCG in Regulating Cell Proliferation and Migration.Medical science monitor : international medical journal of experimental and clinical research · 2016Article
- Novel Insights into the Roles of Rho Kinase in Cancer.Archivum immunologiae et therapiae experimentalis · 2016Review
- CD24 associates with EGFR and supports EGF/EGFR signaling via RhoA in gastric cancer cells.Journal of translational medicine · 2016Article
- Non-muscle myosin II in disease: mechanisms and therapeutic opportunities.Disease models & mechanisms · 2015Review
- ROCK1 as a novel prognostic marker in vulvar cancer.BMC cancer · 2014Article
- Cisplatin and ultra-violet-C synergistically down-regulate receptor tyrosine kinases in human colorectal cancer cells.Molecular cancer · 2012Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRho-associated coiled-coil containing protein kinase (Rho-kinase/ROCK) is involved in various cellular functions including cell proliferation, and is generally considered to be oncogenic, while some studies show that ROCK functions as a negative regulator of cancer progression. As a result, the precise role of ROCK remains controversial. We have previously reported that Rho-kinase/ROCK negatively regulates epidermal growth factor (EGF)-induced cell proliferation in SW480 colon cancer cells. In the present study, we investigated the role of ROCK in EGF receptor (EGFR) signaling in the pancreatic cancer cell lines, Panc1, KP3 and AsPc1.
resultsIn these cells, Y27632, a specific ROCK inhibitor, enhanced EGF-induced BrdU incorporation. The blockade of EGF stimulation utilizing anti-EGFR-neutralizing antibodies suppressed Panc1 cell proliferation. EGF induced RhoA activity, as well as the phosphorylation of cofilin and myosin light chain (MLC), both targets of ROCK signaling, and Y27632 suppressed both of these processes, indicating that the phosphorylation of cofilin and MLC by EGF occurs through ROCK in Panc1 cells. EGF-induced phosphorylation of EGFR at tyrosine residues was augmented when the cells were pretreated with Y27632 or were subjected to gene silencing using ROCK-siRNA. We also obtained similar results using transforming growth factor-α. In addition, EGF-induced phosphorylation of p44/p42 mitogen-activated protein kinase and Akt were also enhanced by Y27632 or ROCK-siRNA. Moreover, an immunofluorescence microscope study revealed that pretreatment with Y27632 delayed EGF-induced internalization of EGFR. Taken together, these data indicate that ROCK functions to switch off EGFR signaling by promoting the internalization of the EGFR.
conclusionsWhile EGF first stimulates the activation of the EGFR and subsequently increases cancer cell proliferation, EGF concurrently induces the activation of ROCK, which then turns off the activated EGFR pathway via a negative feedback system.
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