Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1522083 (Osteosarcoma)
 2,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Osteosarcoma is the most frequent type of primary bone cancer in children and adolescents. These malignant osteoid forming tumors are characterized by their uncontrolled hyperproliferation. Here, we investigate the role of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in the growth of human osteosarcoma. We show that alpha-CaMKII is expressed in human osteosarcoma cell lines and in primary osteosarcoma tissue derived from patients. The pharmacologic inhibition of CaMKII in MG-63 and 143B human osteosarcoma cells by KN-93 resulted in an 80 and 70% decrease in proliferation, respectively, and induced cell cycle arrest in the G(0)/G(1) phase. The in vivo administration of KN-93 to mice xenografted with human osteosarcoma cells significantly decreased intratibial and subcutaneous tumor growth. Mechanistically, KN-93 and alpha-CaMKII siRNA increased p21((CIP/KIP)) gene expression, protein levels, and decreased the phosphorylation of retinoblastoma protein and E2F transactivation. Furthermore, the inhibition of CaMKII decreased membrane-bound Tiam1 and GTP-bound Rac1, which are known to be involved in p21 expression and tumor growth in a variety of solid malignant neoplasms. Our results suggest that CaMKII plays a critical role in the growth of osteosarcoma, and its inhibition could be an attractive therapeutic target to combat conventional high-grade osteosarcoma in children.
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PMID:alpha-CaMKII controls the growth of human osteosarcoma by regulating cell cycle progression. 1763 40

Osteosarcoma is the most common malignant tumor of the bone. The major cause of death in osteosarcoma is the increase in metastatic potential, and the ezrin expression has been correlated with the metastasis development. Ezrin interacts with RhoGDI by dissociating it from RhoGTPases, which allow GTPases to load with GTP, activate RhoA to increase cell migration, and invasion. RhoGTPases have been found to contribute to pathologic processes including cancer cell migration, invasion, and metastasis and overexpression of either the GTPase itself or some elements of Rho signaling that have been detected in many human tumors, including Rac1 and RhoA. We have analyzed Rac1 and RhoA expression in the osteosarcoma tissues to understand the role of the ezrin-Rho family pathway in osteosarcoma metastatic progression. Moreover, we have blocked the ezrin expression using siRNA assay to investigate a possible correlation with RAC1 and RHOA expression in the osteosarcoma cell lines. Our immunohistochemical data showed that many osteosarcomas presented cytoplasmatic positivity for both Rac1 and RhoA and cases, both ezrin positive than ezrin negative, revealed the protein expression of Rac1 and RhoA. The results obtained by ezrin siRNA transfection showed that ezrin expression in the osteosarcoma cell lines might modulate, mainly, the Rac1 expression. It is possible that the mechanism of cell motility mediated by Rac1 and RhoA is maintained in osteosarcomas, and since the expression of ezrin, Rac1 and RhoA do not correlate with metastatic progression in osteosarcoma. However, osteosarcomas without metastasis displayed a positivity for Rac1 and RhoA expression compared with metastatic osteosarcomas and this could be a protective factor.
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PMID:Correlation of the Rac1/RhoA pathway with ezrin expression in osteosarcoma. 2461 49

G protein-coupled receptor 56 (GPR56) is an atypical G protein-coupled receptor, with the long extracellular N-terminus. GPR56 can trigger various downstream signaling responsible for cell survival, proliferation, adhesion, and migration. Expression of GPR56 is associated with cell malignant transformation and tumor cell metastasis in several carcinomas such as melanoma and glioma. Osteosarcoma is the most common malignant bone tumor in adolescents and young adults with high metastasis tendency. The overall survival of osteosarcoma is unsatisfied, partially due to the lacking of predictive markers for metastasis and overall prognosis. This study aimed at figuring out whether expression of the GPR56 was associated with clinicopathological features of osteosarcoma. Eighty-nine patients who received osteosarcoma operation between March 2004 and February 2011 in Linyi People's Hospital were recruited. Immunohistochemical staining (IHC) was carried out to identify the expression of GPR56 in those osteosarcoma tissues, and our cohort was divided into higher-expression group and lower-expression group according to the cut-off of IHC score. Expression of GPR56 in osteosarcoma tissues was correlated with the TNM stage and overall survival. Univariate and multivariate analysis showed that GPR56 could act as an independent prognosis factor for osteosarcoma. Western blot results demonstrated that GPR56-siRNA down-regulated the expression of GTP-RhoA and Ki67. GTP-RhoA participates in the cell migration process, while Ki67 plays important roles in cell proliferation, indicating GPR56 may function in tumor development. Correspondingly, we show that GPR56 regulates the proliferation and invasion capacity of osteosarcoma cells. Our study has revealed the prognostic value of GPR56 expression in osteosarcoma.
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PMID:Expression of G Protein-coupled Receptor 56 Is an Unfavorable Prognostic Factor in Osteosarcoma Patients. 2739 30

Osteosarcoma is a type of aggressive malignant bone tumour that frequently metastasizes to lungs, resulting in poor prognosis. However, the molecular mechanisms of lung metastasis of osteosarcoma remain poorly understood. Here we identify exon-intron fusion genes in osteosarcoma cell lines and tissues. These fusion genes are derived from chromosomal translocations that juxtapose the coding region for amino acids 1-38 of Rab22a (Rab22a1-38) with multiple inverted introns and untranslated regions of chromosome 20. The resulting translation products, designated Rab22a-NeoFs, acquire the ability to drive lung metastasis of osteosarcoma. The Rab22a1-38 moiety governs the function of Rab22a-NeoFs by binding to SmgGDS-607, a GTP-GDP exchange factor of RhoA. This association facilitates the release of GTP-bound RhoA from SmgGDS-607, which induces increased activity of RhoA and promotes metastasis. Disrupting the interaction between Rab22a-NeoF1 and SmgGDS-607 with a synthetic peptide prevents lung metastasis in an orthotopic model of osteosarcoma. Our findings may provide a promising strategy for a subset of osteosarcoma patients with lung metastases.
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PMID:Chromosomal translocation-derived aberrant Rab22a drives metastasis of osteosarcoma. 3252 25