{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nROCK2 is emerging as a pivotal effector in cancer‐related processes, modulating cytoskeletal reorganization, cell migration, invasion, and proliferation. In several malignancies—including hepatocellular, squamous, osteosarcoma, non–small cell lung, and neuroblastoma—ROCK2 overexpression or hyperactivation drives metastatic progression through the regulation of focal adhesion dynamics, cell–cell junction disassembly, and cleavage furrow formation during cytokinesis. Moreover, oncogenic microRNAs such as miR‐138, miR‐200b/200c/429, miR‐144, miR‐101, and miR‐126 have been shown to target ROCK2 directly, resulting in impaired stress fiber formation, altered cell morphology, and suppression of invasive behavior. These findings highlight that ROCK2 functions as a central mediator of tumor progression by integrating diverse upstream signals—ranging from Notch1/p53 and Plk1 to RhoA—to induce downstream effects on actomyosin contractility and cancer cell motility."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the vasculature and related contexts, ROCK2 plays a key role in modulating smooth muscle cell contractility and vascular tone, as well as in the regulation of endothelial permeability and inflammatory responses. ROCK2 contributes to vascular smooth muscle contraction by directly binding to myosin phosphatase components, thereby enhancing myosin light chain phosphorylation. Genetic variations in ROCK2 are linked to higher blood pressure and increased systemic vascular resistance, while ROCK2‐dependent signaling is also involved in endothelial cell activation—mediating adhesion molecule expression via NF‐κB signaling—and in fibroblast activation associated with vascular remodeling. Additionally, pharmacological inhibition of ROCK2 has been shown to decrease invasive cell behavior in models of melanoma, pancreatic cancer, and pulmonary hypertension, underscoring its promise as a therapeutic target in cardiovascular disease and tumor vascularization."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "19", "end_ref": "33"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in oncogenesis and vascular regulation, ROCK2 is central to the control of diverse cellular structural and signaling events. High‐resolution structural studies have revealed that ROCK2 operates as a constitutive dimer with a long coiled‐coil region acting as a molecular ruler, thereby confining its kinase activity to specific cytoskeletal domains. In many tissues, ROCK2 exhibits distinct subcellular distributions that underlie its isoform‐specific functions—including the phosphorylation of nonmuscle myosin regulatory light chain, regulation of actin turnover via cofilin phosphorylation, and modulation of nuclear transport through phosphorylation of nucleoporins. Furthermore, ROCK2 signaling in neurons has been linked to the regulation of mitophagy and to protein complexes that maintain centrosome integrity, as well as to mechanisms contributing to tau processing. These multifaceted roles not only underscore the importance of ROCK2 in maintaining normal cell architecture and function but also point to its potential as a therapeutic target in neurodegenerative disorders and other pathologies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "34", "end_ref": "44"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Carmen Chak-Lui Wong, Chun-Ming Wong, Edmund Kwok-Kwun Tung, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Downregulation of the Rho GTPase signaling pathway is involved in the microRNA-138-mediated inhibition of cell migration and invasion in tongue squamous cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cancer (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ijc.25320"}], "href": "https://doi.org/10.1002/ijc.25320"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20232393"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20232393"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Carmen Chak-Lui Wong, Chun-Ming Wong, Edmund Kwok-Kwan Tung, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "The expression and prognostic value of ROCK I and ROCK II and their role in human breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Oncol (2008)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18695890"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18695890"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Stanislav N Samarin, Andrei I Ivanov, Gilles Flatau, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rho/Rho-associated kinase-II signaling mediates disassembly of epithelial apical junctions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.e07-04-0315"}], "href": "https://doi.org/10.1091/mbc.e07-04-0315"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17596509"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17596509"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "I Y Yotova, P Quan, N Leditznig, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Abnormal activation of Ras/Raf/MAPK and RhoA/ROCKII signalling pathways in eutopic endometrial stromal cells of patients with endometriosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Reprod (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/humrep/der010"}], "href": "https://doi.org/10.1093/humrep/der010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21303778"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21303778"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Frances E Lock, Neil A Hotchin "}, {"type": "b", "children": [{"type": "t", "text": "Distinct roles for ROCK1 and ROCK2 in the regulation of keratinocyte differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0008190"}], "href": "https://doi.org/10.1371/journal.pone.0008190"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19997641"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19997641"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Chun-Ming Wong, Lai Wei, Sandy Leung-Kuen Au, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Downregulation of miR-101 contributes to epithelial-mesenchymal transition in cisplatin resistance of NSCLC cells by targeting ROCK2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.6852"}], "href": "https://doi.org/10.18632/oncotarget.6852"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27229528"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27229528"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Jonathan M Weiss, Wei Chen, Melanie S Nyuydzefe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ROCK2 signaling is required to induce a subset of T follicular helper cells through opposing effects on STATs in autoimmune settings."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Signal (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/scisignal.aad8953"}], "href": "https://doi.org/10.1126/scisignal.aad8953"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27436361"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27436361"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Yuepeng Wang, Xiaoyu Rayne Zheng, Nadeene Riddick, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ROCK isoform regulation of myosin phosphatase and contractility in vascular smooth muscle cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCRESAHA.108.188524"}], "href": "https://doi.org/10.1161/CIRCRESAHA.108.188524"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19131646"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19131646"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Zhulanqiqige Do e, Yoshihiro Fukumoto, Aya Takaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Evidence for Rho-kinase activation in patients with pulmonary arterial hypertension."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ J (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1253/circj.cj-09-0135"}], "href": "https://doi.org/10.1253/circj.cj-09-0135"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19590140"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19590140"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Alfiya Akhmetshina, Clara Dees, Margarita Pileckyte, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rho-associated kinases are crucial for myofibroblast differentiation and production of extracellular matrix in scleroderma fibroblasts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arthritis Rheum (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/art.23677"}], "href": "https://doi.org/10.1002/art.23677"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18668558"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18668558"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Nicola Rath, Jennifer P Morton, Linda Julian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ROCK signaling promotes collagen remodeling to facilitate invasive pancreatic ductal adenocarcinoma tumor cell growth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO Mol Med (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/emmm.201606743"}], "href": "https://doi.org/10.15252/emmm.201606743"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28031255"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28031255"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Toru Shimizu, Yoshihiro Fukumoto, Shin-Ichi Tanaka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Crucial role of ROCK2 in vascular smooth muscle cells for hypoxia-induced pulmonary hypertension in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arterioscler Thromb Vasc Biol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/ATVBAHA.113.301357"}], "href": "https://doi.org/10.1161/ATVBAHA.113.301357"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24135024"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24135024"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Amine Sadok, Afshan McCarthy, John Caldwell, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rho kinase inhibitors block melanoma cell migration and inhibit metastasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-14-2156"}], "href": "https://doi.org/10.1158/0008-5472.CAN-14-2156"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25840982"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25840982"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Hideaki Shimada, Lakshman E Rajagopalan "}, {"type": "b", "children": [{"type": "t", "text": "Rho kinase-2 activation in human endothelial cells drives lysophosphatidic acid-mediated expression of cell adhesion molecules via NF-kappaB p65."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.099630"}], "href": "https://doi.org/10.1074/jbc.M109.099630"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20164172"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20164172"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Toru Shimizu, James K Liao "}, {"type": "b", "children": [{"type": "t", "text": "Rho Kinases and Cardiac Remodeling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ J (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1253/circj.CJ-16-0433"}], "href": "https://doi.org/10.1253/circj.CJ-16-0433"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27251065"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27251065"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Jia Yin, Fu-Shin X Yu "}, {"type": "b", "children": [{"type": "t", "text": "Rho kinases regulate corneal epithelial wound healing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Cell Physiol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpcell.90624.2007"}], "href": "https://doi.org/10.1152/ajpcell.90624.2007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18495812"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18495812"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Mian He, Yang Cheng, Wen Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Vascular endothelial growth factor C promotes cervical cancer metastasis via up-regulation and activation of RhoA/ROCK-2/moesin cascade."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Cancer (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2407-10-170"}], "href": "https://doi.org/10.1186/1471-2407-10-170"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20429915"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20429915"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Tammy M Seasholtz, Jennifer Wessel, Fangwen Rao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rho kinase polymorphism influences blood pressure and systemic vascular resistance in human twins: role of heredity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hypertension (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/01.HYP.0000217364.45622.f0"}], "href": "https://doi.org/10.1161/01.HYP.0000217364.45622.f0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16585408"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16585408"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Natalia V Bogatcheva, Djanybek Adyshev, Bolot Mambetsariev, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Involvement of microtubules, p38, and Rho kinases pathway in 2-methoxyestradiol-induced lung vascular barrier dysfunction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Lung Cell Mol Physiol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajplung.00217.2006"}], "href": "https://doi.org/10.1152/ajplung.00217.2006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17012370"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17012370"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Keiji Oi, Hiroaki Shimokawa, Junko Hiroki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Remnant lipoproteins from patients with sudden cardiac death enhance coronary vasospastic activity through upregulation of Rho-kinase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arterioscler Thromb Vasc Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/01.ATV.0000126678.93747.80"}], "href": "https://doi.org/10.1161/01.ATV.0000126678.93747.80"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15044207"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15044207"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Xiaowei Shi, Wenjing Yu, Tiantian Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Panax notoginseng saponins provide neuroprotection by regulating NgR1/RhoA/ROCK2 pathway expression, in vitro and in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Ethnopharmacol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jep.2016.06.017"}], "href": "https://doi.org/10.1016/j.jep.2016.06.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27288754"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27288754"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Andrei I Ivanov, Stanislav N Samarin, Moshe Bachar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protein kinase C activation disrupts epithelial apical junctions via ROCK-II dependent stimulation of actomyosin contractility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Cell Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2121-10-36"}], "href": "https://doi.org/10.1186/1471-2121-10-36"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19422706"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19422706"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Hiroto Yamaguchi, Miyuki Kasa, Mutsuki Amano, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular mechanism for the regulation of rho-kinase by dimerization and its inhibition by fasudil."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Structure (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.str.2005.11.024"}], "href": "https://doi.org/10.1016/j.str.2005.11.024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16531242"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16531242"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Natalia Moskal, Victoria Riccio, Mikhail Bashkurov, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ROCK inhibitors upregulate the neuroprotective Parkin-mediated mitophagy pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-019-13781-3"}], "href": "https://doi.org/10.1038/s41467-019-13781-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31900402"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31900402"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Kozue Ueda, Maki Murata-Hori, Masaaki Tatsuka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rho-kinase contributes to diphosphorylation of myosin II regulatory light chain in nonmuscle cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.onc.1205747"}], "href": "https://doi.org/10.1038/sj.onc.1205747"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12185584"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12185584"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Yueting Peng, Zhongyuan Chen, Yu Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ROCK isoforms differentially modulate cancer cell motility by mechanosensing the substrate stiffness."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Biomater (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.actbio.2019.02.015"}], "href": "https://doi.org/10.1016/j.actbio.2019.02.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30771534"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30771534"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Frances E Lock, Katie R Ryan, Natalie S Poulter, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential regulation of adhesion complex turnover by ROCK1 and ROCK2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0031423"}], "href": "https://doi.org/10.1371/journal.pone.0031423"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22348083"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22348083"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Erik G Gentry, Benjamin W Henderson, Andrew E Arrant, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rho Kinase Inhibition as a Therapeutic for Progressive Supranuclear Palsy and Corticobasal Degeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.2336-15.2016"}], "href": "https://doi.org/10.1523/JNEUROSCI.2336-15.2016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26818518"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26818518"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "Masaharu Hazawa, De-Chen Lin, Akiko Kobayashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ROCK-dependent phosphorylation of NUP62 regulates p63 nuclear transport and squamous cell carcinoma proliferation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embr.201744523"}], "href": "https://doi.org/10.15252/embr.201744523"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29217659"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29217659"}]}, {"type": "r", "ref": 41, "children": [{"type": "t", "text": "Mario A Shields, Seth B Krantz, David J Bentrem, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interplay between β1-integrin and Rho signaling regulates differential scattering and motility of pancreatic cancer cells by snail and Slug proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.308940"}], "href": "https://doi.org/10.1074/jbc.M111.308940"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22232555"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22232555"}]}, {"type": "r", "ref": 42, "children": [{"type": "t", "text": "Linda Truebestein, Daniel J Elsner, Elisabeth Fuchs, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A molecular ruler regulates cytoskeletal remodelling by the Rho kinases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms10029"}], "href": "https://doi.org/10.1038/ncomms10029"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26620183"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26620183"}]}, {"type": "r", "ref": 43, "children": [{"type": "t", "text": "Jian Wu, Jibo Liu, Yaqin Ding, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiR-455-3p suppresses renal fibrosis through repression of ROCK2 expression in diabetic nephropathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2018.06.105"}], "href": "https://doi.org/10.1016/j.bbrc.2018.06.105"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29932921"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29932921"}]}, {"type": "r", "ref": 44, "children": [{"type": "t", "text": "Hui-Feng Wang, Katsuya Takenaka, Akira Nakanishi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BRCA2 and nucleophosmin coregulate centrosome amplification and form a complex with the Rho effector kinase ROCK2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-10-0030"}], "href": "https://doi.org/10.1158/0008-5472.CAN-10-0030"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21084279"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21084279"}]}]}]}