ArticleJapanese journal of cancer research : Gann2001
Small GTP-binding protein, Rho, both increased and decreased cellular motility, activation of matrix metalloproteinase 2 and invasion of human osteosarcoma cells.
Article in Japanese journal of cancer research : Gann, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 59 citations in OpenAlex.
- Targeting protein geranylgeranylation slows tumor development in a murine model of prostate cancer metastasis.Cancer biology & therapy · 2017Trial
- Effect of oxLDL on transcriptional expression of human lens epithelial cells.International journal of clinical and experimental pathology · 2020Article
- Lysophosphatidic acid activates the RhoA and NF-κB through Akt/IκBα signaling and promotes prostate cancer invasion and progression by enhancing functional invadopodia formation.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Interventional Transcatheter Closure Ameliorates the Leukocyte Rho Kinase Activities among Patients with Patent Ductus Arteriosus.Acta Cardiologica Sinica · 2015Article
- Targeting geranylgeranylation reduces adrenal gland tumor burden in a murine model of prostate cancer metastasis.Clinical & experimental metastasis · 2015Article
- In vitro studies in a myelogenous leukemia cell line suggest an organized binding of geranylgeranyl diphosphate synthase inhibitors.Biochemical pharmacology · 2015Article
- VAV3 oncogene expression in colorectal cancer: clinical aspects and functional characterization.Scientific reports · 2015Article
- Role of the VEGF-Flt-1-FAK pathway in the pathogenesis of osteoclastic bone destruction of giant cell tumors of bone.Journal of orthopaedic surgery and research · 2010Article
- Basic fibroblast growth factor in the bone microenvironment enhances cell motility and invasion of Ewing's sarcoma family of tumours by activating the FGFR1-PI3K-Rac1 pathway.British journal of cancer · 2010Article
- Reduction of hyaluronan-CD44-mediated growth, migration, and cisplatin resistance in head and neck cancer due to inhibition of Rho kinase and PI-3 kinase signaling.Archives of otolaryngology--head & neck surgery · 2010Article
- Guanine nucleotide exchange factor-H1 regulates cell migration via localized activation of RhoA at the leading edge.Molecular biology of the cell · 2009Article
- Blockade of the RhoA-JNK-c-Jun-MMP2 cascade by atorvastatin reduces osteosarcoma cell invasion.The Journal of biological chemistry · 2008Article
- Focal adhesion kinase is activated in invading fibrosarcoma cells and regulates metastasis.Clinical & experimental metastasis · 2005Article
- Expression and significance of RhoC gene in hepatocellular carcinoma.World journal of gastroenterology · 2003Article
- STAT5a activation mediates the epithelial to mesenchymal transition induced by oncogenic RhoA.Molecular biology of the cell · 2003Article
- Cell growth and metastasis in pancreatic cancer: is Vav the Rho'd to activation?International journal of gastrointestinal cancer · 2002Review
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6 authors at 1 institution in 1 country.
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Abstract
Rho, a member of the small GTP-binding proteins, and one of its downstream effectors ROCK (Rho-associated coiled-coil forming protein kinase) play an important role in the invasion of tumor cells. Lysophosphatidic acid (LPA) activates Rho and ROCK and promotes the organization of stress fibers and focal adhesions. However, the effect of LPA on tumor cell invasion is still controversial. In the present study, human osteosarcoma cells treated with a high concentration of LPA (high LPA) showed considerable formation of stress fibers and focal adhesions compared to the cells treated with a low concentration of LPA (low LPA). C3 (inhibitor of Rho) or Y27632 (an inhibitor of ROCK) inhibited the effects of LPA, indicating that LPA activates the Rho-ROCK pathway in the cells. In addition, Rho activation assay showed that the activation level of Rho can be altered by changing the concentration of LPA. Low LPA stimulated the motility and invasion of the cells, while high LPA reduced both. The disruption of extracellular matrix (ECM) by matrix metalloproteinase 2 (MMP2) is also critical for tumor cell invasion. MMP2 is activated by membranous type-1 MMP (MT1-MMP) and type-2 tissue inhibitor of MMP (TIMP2). High LPA suppressed the activation of MMP2 through down-regulation of MT1-MMP and TIMP2. C3 and Y27632 reversed the suppression of the activation of MMP2 and expression of MT1-MMP and TIMP2, suggesting the involvement of the Rho-ROCK pathway in ECM degradation. Tyrosine phosphorylation of focal adhesion kinase (FAK) was also required for the invasion of tumor cells to occur. Low LPA enhanced the tyrosine phosphorylation of FAK whereas high LPA reduced it. In conclusion, we suggest that Rho has a dual effect on the invasion of osteosarcoma cells by modulating the motility, the ability to degrade ECM and tyrosine phosphorylation of FAK.
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