ArticlePloS one2017
Inhibition of ROCK1 kinase modulates both tumor cells and stromal fibroblasts in pancreatic cancer.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 79 citations in OpenAlex.
- Migrasome and cancer - from cellular to clinical perspectives.Biomarker research · 2026Review
- Targeting Cancer-Associated Fibroblasts with Small-Molecule Inhibitors: Molecular Mechanisms and Therapeutic Potential.Drug design, development and therapy · 2026Review
- MULGONET: An interpretable neural network framework to integrate multi-omics data for cancer recurrence prediction and biomarker discovery.Fundamental research · 2026Article
- Extracellular matrix stiffness in endometrial cancer: driving progression and modulating treatment sensitivity via the ROCK1/YAP1 axis.Cell death & disease · 2025Article
- Review
- Cancer associated fibroblasts in cancer development and therapy.Journal of hematology & oncology · 2025Review
- Mechanical forces in the tumor microenvironment: roles, pathways, and therapeutic approaches.Journal of translational medicine · 2025Review
- Identifying key genes in cancer networks using persistent homology.Scientific reports · 2025Article
- Unveiling the resistance to therapies in pancreatic ductal adenocarcinoma.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2024Review
- Development of Novel ROCK Inhibitors via 3D-QSAR and Molecular Docking Studies: A Framework for Multi-Target Drug Design.Pharmaceutics · 2024Article
- Non-Muscle Myosin II A: Friend or Foe in Cancer?International journal of molecular sciences · 2024Review
- Targeting endocytosis to sensitize cancer cells to programmed cell death.Biochemical Society transactions · 2024Review
- Focus on Pancreatic Cancer Microenvironment.Current oncology (Toronto, Ont.) · 2024Review
- Review
- Identification and Validation of the Anoikis-Related Gene Signature as a Novel Prognostic Model for Cervical Squamous Cell Carcinoma, Endocervical Adenocarcinoma, and Revelation Immune Infiltration.Medicina (Kaunas, Lithuania) · 2023Article
- The role of RAS oncogenes in controlling epithelial mechanics.Trends in cell biology · 2023Review
- A primer on cancer-associated fibroblast mechanics and immunosuppressive ability.Exploration of targeted anti-tumor therapy · 2023Article
- Rho-associated kinase1 promotes laryngeal squamous cell carcinoma tumorigenesis and progression via the FAK signaling pathway.Discover oncology · 2022Article
- Rigid Tissue Increases Cytoplasmic pYAP Expression in Pre-Malignant Stage of Lung Squamous Cell Carcinoma (SCC) In Vivo.Current issues in molecular biology · 2022Article
- Prenatal diagnosis and genetic counseling of a paternally inherited microduplication 18q11.1 to 18q11.2 in a chinese family.Molecular cytogenetics · 2022Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
ROCK, or Rho-associated coiled coil-containing protein kinase, is a member of the AGC kinase family and has been shown to play a role in cell migration, ECM synthesis, stress-fiber assembly, and cell contraction. Increased ROCK expression has been reported in multiple pathological conditions, including cancer. Here, we report increased expression of ROCK 1 in pancreatic tumor epithelial cells as well as in cancer associated fibroblasts (CAF). In our analysis, 62% of tumor samples exhibited ≥2+ in staining intensity by IHC analysis, versus 40% of adjacent normal tissue samples (P<0.0001). Thus, we hypothesized that ROCKs may play a significant role in pancreatic cancer progression, and may serve as a suitable target for treatment. We report a low frequency (4/34) amplification of the ROCK1 gene locus at chromosome 18q11.1 in pancreatic ductal adenocarcinoma (PDAC) patient tissue samples by aCGH analysis. Inhibition of ROCK kinase activity by a small molecule inhibitor (fasudil) resulted in moderate (IC50s of 6-71 μM) inhibition of PDAC cell proliferation, migration, and activation of co-cultured stellate cells. In the KPC mouse model for pancreatic cancer, fasudil decreased tumor collagen deposition. This translated to an enhanced overall survival of the mice and an increase in gemcitabine uptake. Though fasudil may target both the tumor epithelial cells and the CAFs, our findings are consistent with the hypothesis that inhibition of tumor stroma enhances drug penetration and efficacy in PDAC. Overall, our data suggests that ROCK1 may serve as a potential therapeutic target to enhance current treatment regimens for pancreatic cancer.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.