u-0126 has been researched along with Rhabdomyosarcoma--Alveolar* in 2 studies
2 other study(ies) available for u-0126 and Rhabdomyosarcoma--Alveolar
Article | Year |
---|---|
MET/ERK2 pathway regulates the motility of human alveolar rhabdomyosarcoma cells.
In alveolar rhabdomyosarcoma (ARMS) that is a highly malignant pediatric soft tissue tumor, MET, a receptor of hepatocyte growth factor (HGF), was reported to be downstream of the PAX3-FOXO1 fusion gene specific to ARMS, and a key mediator of metastatic behavior in RMS. So far, no studies have investigated the downstream signaling pathways of MET in ARMS, even though HGF and MET have been suggested to be deeply involved in the invasiveness of ARMS. In this study, we demonstrated the functions of MET signaling in ARMS in vitro by using three human ARMS cell lines and three human embryonal rhabdomyosarcoma (ERMS) cell lines. MET mRNA levels and MET protein expression in ARMS cell lines was higher than those in ERMS cell lines as detected by real-time quantitative PCR and western blotting, respectively. Based on cell growth and cell cycle analyses it was found that HGF stimulation did not enhance the proliferation of ERMS or ARMS cell lines. HGF-stimulated cell motility of ARMS cell lines was inhibited by U0126 (ERK1/2 inhibitor) but was only partially inhibited by PD98059 (ERK1 inhibitor) or rapamycin (mTOR inhibitor) as observed in wound-healing and migration assays. Western blotting revealed that ERK1/2 was dephosphorylated by U0126 to a higher extent than by PD98059 in the ARMS cells. HGF-stimulated cell motility of Rh30 cell line was inhibited not by ERK1 siRNA, but by ERK2 siRNA. Our data thus suggest that HGF/MET signaling promotes motility of ARMS cells mainly through ERK2 signaling. A specific inhibitor of ERK2 phosphorylation could therefore be a specific anticancer agent against invasiveness and metastasis in ARMS. Topics: Butadienes; Cell Line, Tumor; Cell Movement; Cell Proliferation; Hep G2 Cells; Hepatocyte Growth Factor; Humans; MAP Kinase Signaling System; Mitogen-Activated Protein Kinase 1; Nitriles; Proto-Oncogene Proteins c-met; Rhabdomyosarcoma, Alveolar; RNA, Small Interfering; Signal Transduction | 2017 |
DNMT3B in vitro knocking-down is able to reverse embryonal rhabdomyosarcoma cell phenotype through inhibition of proliferation and induction of myogenic differentiation.
Aberrant DNA methylation has been frequently observed in many human cancers, including rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children. To date, the expression and function of the de novo DNA methyltransferase (DNMT) 3B in RMS have not yet been investigated. Our study show for the first time a significant up-regulation of DNMT3B levels in 14 RMS tumour samples and 4 RMS cell lines in comparison to normal skeletal muscle. Transfection of RD and TE671 cells, two in vitro models of embryonal RMS (ERMS), with a synthetic DNMT3B siRNA decreased cell proliferation by arresting cell cycle at G1 phase, as demonstrated by the reduced expression of Cyclin B1, Cyclin D1 and Cyclin E2, and by the concomitant up-regulation of the checkpoint regulators p21 and p27. DNMT3B depletion also impaired RB phosphorylation status and decreased migratory capacity and clonogenic potential. Interestingly, DNMT3B knock-down was able to commit ERMS cells towards myogenic terminal differentiation, as confirmed by the acquisition of a myogenic-like phenotype and by the increased expression of the myogenic markers MYOD1, Myogenin and MyHC. Finally, inhibition of MEK/ERK signalling by U0126 resulted in a reduction of DNMT3B protein, giving evidence that DNMT3B is a down-stream molecule of this oncogenic pathway.Taken together, our data indicate that altered expression of DNMT3B plays a key role in ERMS development since its silencing is able to reverse cell cancer phenotype by rescuing myogenic program. Epigenetic therapy, by targeting the DNA methylation machinery, may represent a novel therapeutic strategy against RMS. Topics: Butadienes; Cell Cycle; Cell Differentiation; Cell Line, Tumor; Cell Proliferation; DNA (Cytosine-5-)-Methyltransferases; DNA Methyltransferase 3B; Down-Regulation; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Humans; In Vitro Techniques; Muscle Fibers, Skeletal; Nitriles; Phenotype; Rhabdomyosarcoma, Alveolar; Rhabdomyosarcoma, Embryonal | 2016 |