ArticleOncotarget2016
RhoE/ROCK2 regulates chemoresistance through NF-κB/IL-6/ STAT3 signaling in hepatocellular carcinoma.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 37 citations in OpenAlex.
- Phosphoproteomic Data Integration Reveals Paralog-Specific Co-Regulatory Networks of Rho-Associated Kinases ROCK1 and ROCK2.International journal of molecular sciences · 2026Article
- Review
- GPR56/ADGRG1 induces biased Rho-ROCK-MLC and JAK-STAT3 signaling to promote amoeboid-like morphology and IL-6 upregulation in melanoma cells.Cell communication and signaling : CCS · 2025Article
- Intercellular contractile force attenuates chemosensitivity through Notch-MVP-mediated nuclear drug export.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Cell hiding in colorectal cancer: correlation with response to chemotherapy in vitro and in vivo.Scientific reports · 2024Article
- Synthesis, Docking, and Machine Learning Studies of Some Novel Quinolinesulfonamides-Triazole Hybrids with Anticancer Activity.Molecules (Basel, Switzerland) · 2024Article
- The Specific ROCK2 Inhibitor KD025 Alleviates Glycolysis through Modulating STAT3-, CSTA- and S1PR3-Linked Signaling in Human Trabecular Meshwork Cells.Biomedicines · 2024Article
- Loss of RND3/RHOE controls entosis through LAMP1 expression in hepatocellular carcinoma.Cell death & disease · 2024Article
- Deciphering STAT3 signaling potential in hepatocellular carcinoma: tumorigenesis, treatment resistance, and pharmacological significance.Cellular & molecular biology letters · 2023Review
- Rho Kinase Inhibitor Y27632 Improves Recovery After Spinal Cord Injury by Shifting Astrocyte Phenotype and Morphology via the ROCK/NF-κB/C3 Pathway.Neurochemical research · 2022Article
- RHO GTPase family in hepatocellular carcinoma.Experimental hematology & oncology · 2022Review
- The Roles of microRNA miR-185 in Digestive Tract Cancers.Non-coding RNA · 2022Review
- Mechanical Stretch Promotes Macrophage Polarization and Inflammation via the RhoA-ROCK/NF-BioMed research international · 2022Article
- GASC1 promotes hepatocellular carcinoma progression by inhibiting the degradation of ROCK2.Cell death & disease · 2021Article
- LncRNA PITPNA-AS1 as a Potential Diagnostic Marker and Therapeutic Target Promotes Hepatocellular Carcinoma Progression via Modulating miR-448/ROCK1 Axis.Frontiers in medicine · 2021Article
- The Crosstalk Between Regulatory Non-Coding RNAs and Nuclear Factor Kappa B in Hepatocellular Carcinoma.Frontiers in oncology · 2021Review
- Epidermal ROCK2 induces AKT1/GSK3β/β-catenin, NFκB and dermal tenascin C; but enhanced differentiation and p53/p21 inhibit papilloma.Carcinogenesis · 2020Article
- Ingenuity pathway analysis of differentially expressed genes involved in signaling pathways and molecular networks in RhoE gene‑edited cardiomyocytes.International journal of molecular medicine · 2020Article
- RhoC regulates radioresistance via crosstalk of ROCK2 with the DNA repair machinery in cervical cancer.Journal of experimental & clinical cancer research : CR · 2019Article
- miR-185-5p targets ROCK2 and inhibits cell migration and invasion of hepatocellular carcinoma.Oncology letters · 2019Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Small Rho GTPase (Rho) and its immediate effector Rho kinase (ROCK) are reported to regulate cell survival, but the detailed molecular mechanism remains largely unknown. We had previously shown that Rho/ROCK signaling was highly activated in hepatocellular carcinoma (HCC). In this study, we further demonstrated that downregulation of RhoE, a RhoA antagonist, and upregulation of ROCK enhanced resistance to chemotherapy in HCC in both in vitro cell and in vivo murine xenograft models, whereas a ROCK inhibitor was able to profoundly sensitize HCC tumors to cisplatin treatment. Specifically, the ROCK2 isoform but not ROCK1 maintained the chemoresistance in HCC cells. Mechanistically, we demonstrated that activation of ROCK2 enhanced the phosphorylation of JAK2 and STAT3 through increased expression of IL-6 and the IL-6 receptor complex. We also identified IKKβ as the direct downstream target of Rho/ROCK, and activation of ROCK2 significantly augmented NF-κB transcription activity and induced IL-6 expression. These data indicate that Rho/ROCK signaling activates a positive feedback loop of IKKβ/NF-κB/IL-6/STAT3 which confers chemoresistance to HCC cells and is a potential molecular target for HCC therapy.
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Registered trials
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.