scholarly journals DNMT3Bin vitroknocking-down is able to reverse embryonal rhabdomyosarcoma cell phenotype through inhibition of proliferation and induction of myogenic differentiation

Oncotarget ◽  
2016 ◽  
Vol 7 (48) ◽  
pp. 79342-79356 ◽  
Author(s):  
Francesca Megiorni ◽  
Simona Camero ◽  
Simona Ceccarelli ◽  
Heather P. McDowell ◽  
Olga Mannarino ◽  
...  
Keyword(s):  
Myogenic Differentiation ◽  
Embryonal Rhabdomyosarcoma ◽  
Cell Phenotype ◽  
Inhibition Of Proliferation ◽  
Rhabdomyosarcoma Cell

scholarly journals AKT and PAX3-FKHR cooperation enforces myogenic differentiation blockade in alveolar rhabdomyosarcoma cell

Cell Cycle ◽  
2012 ◽  
Vol 11 (5) ◽  
pp. 895-908 ◽  
Author(s):  
Mathivanan Jothi ◽  
Kochi Nishijo ◽  
Charles Keller ◽  
Asoke K. Mal
Keyword(s):  
Myogenic Differentiation ◽  
Alveolar Rhabdomyosarcoma ◽  
Rhabdomyosarcoma Cell

scholarly journals Inhibition of the histone demethylase, KDM5B, directly induces re-expression of tumor suppressor protein HEXIM1 in cancer cells

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Monica M. Montano ◽  
I-Ju Yeh ◽  
Yinghua Chen ◽  
Chris Hernandez ◽  
Janna G. Kiselar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Critical Role ◽  
Cell Phenotype ◽  
Relative Role ◽  
Western Blots ◽  
Inhibition Of Proliferation ◽  
Proliferation Assays

Abstract Background The tumor suppressor actions of hexamethylene bis-acetamide (HMBA)-inducible protein 1 (HEXIM1) in the breast, prostate, melanomas, and AML have been reported by our group and others. Increased HEXIM1 expression caused differentiation and inhibited proliferation and metastasis of cancer cells. Historically, HEXIM1 has been experimentally induced with the hybrid polar compound HMBA, but HMBA is a poor clinical candidate due to lack of a known target, poor pharmacological properties, and unfavorable ADMETox characteristics. Thus, HEXIM1 induction is an intriguing therapeutic approach to cancer treatment, but requires better chemical tools than HMBA. Methods We identified and verified KDM5B as a target of HEXIM1 inducers using a chemical proteomics approach, biotin–NeutrAvidin pull-down assays, surface plasmon resonance, and molecular docking. The regulation of HEXIM1 by KDM5B and KDM5B inhibitors was assessed using chromatin immunoprecipitation assays, RT-PCR, western blotting, and depletion of KDM5B with shRNAs. The regulation of breast cancer cell phenotype by KDM5B inhibitors was assessed using western blots, differentiation assays, proliferation assays, and a mouse model of breast cancer metastasis. The relative role of HEXIM1 in the action of KDM5B inhibitors was determined by depleting HEXIM1 using shRNAs followed by western blots, differentiation assays, and proliferation assays. Results We have identified a highly druggable target, KDM5B, which is inhibited by small molecule inducers of HEXIM1. RNAi knockdown of KDM5B induced HEXIM1 expression, thus validating the specific negative regulation of tumor suppressor HEXIM1 by the H3K4me3/2 demethylase KDM5B. Known inhibitors of KDM5B were also able to induce HEXIM1 expression, inhibit cell proliferation, induce differentiation, potentiate sensitivity to cancer chemotherapy, and inhibit breast tumor metastasis. Conclusion HMBA and 4a1 induce HEXIM1 expression by inhibiting KDM5B. Upregulation of HEXIM1 expression levels plays a critical role in the inhibition of proliferation of breast cancer cells using KDM5B inhibitors. Based on the novel molecular scaffolds that we identified which more potently induced HEXIM1 expression and data in support that KDM5B is a target of these compounds, we have opened up new lead discovery and optimization directions.

scholarly journals Characterization of a New Human Embryonal Rhabdomyosarcoma Cell Line, RMS-GR

1998 ◽  
Vol 89 (5) ◽  
pp. 525-532 ◽  
Author(s):  
Juan Emilio Fernández ◽  
Jose Prados ◽  
Consolación Melguizo ◽  
Nicola Arena ◽  
Fabio Malavasi ◽  
...  
Keyword(s):  
Cell Line ◽  
Embryonal Rhabdomyosarcoma ◽  
Rhabdomyosarcoma Cell Line ◽  
Rhabdomyosarcoma Cell

c-Myc Sustains Transformed Phenotype and Promotes Radioresistance of Embryonal Rhabdomyosarcoma Cell Lines

2016 ◽  
Vol 185 (4) ◽  
pp. 411-422 ◽  
Author(s):  
G. L. Gravina ◽  
C. Festuccia ◽  
V. M. Popov ◽  
A. Di Rocco ◽  
A. Colapietro ◽  
...  
Keyword(s):  
Cell Lines ◽  
Embryonal Rhabdomyosarcoma ◽  
Rhabdomyosarcoma Cell

scholarly journals EHMT2 epigenetically suppresses Wnt signaling and is a potential target in embryonal rhabdomyosarcoma

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Ananya Pal ◽  
Jia Yu Leung ◽  
Gareth Chin Khye Ang ◽  
Vinay Kumar Rao ◽  
Luca Pignata ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Myogenic Differentiation ◽  
Embryonal Rhabdomyosarcoma ◽  
Differentiation Therapy ◽  
Canonical Wnt Signaling ◽  
Therapeutic Modalities ◽  
Xenograft Models ◽  
Canonical Wnt

Wnt signaling is downregulated in embryonal rhabdomyosarcoma (ERMS) and contributes to the block of differentiation. Epigenetic mechanisms leading to its suppression are unknown and could pave the way toward novel therapeutic modalities. We demonstrate that EHMT2 suppresses canonical Wnt signaling by activating expression of the Wnt antagonist DKK1. Inhibition of EHMT2 expression or activity in human ERMS cell lines reduced DKK1 expression and elevated canonical Wnt signaling resulting in myogenic differentiation in vitro and in mouse xenograft models in vivo. Mechanistically, EHMT2 impacted Sp1 and p300 enrichment at the DKK1 promoter. The reduced tumor growth upon EHMT2 deficiency was reversed by recombinant DKK1 or LGK974, which also inhibits Wnt signaling. Consistently, among 13 drugs targeting chromatin modifiers, EHMT2 inhibitors were highly effective in reducing ERMS cell viability. Our study demonstrates that ERMS cells are vulnerable to EHMT2 inhibitors and suggest that targeting the EHMT2-DKK1-β-catenin node holds promise for differentiation therapy.

Characterization of an embryonal rhabdomyosarcoma cell line showing amplification and over-expression of the N-myc oncogene

1990 ◽  
Vol 45 (4) ◽  
pp. 705-711 ◽  
Author(s):  
Yasuhide Hayashi ◽  
Tohru Sugimoto ◽  
Yoshihiro Horii ◽  
Hajime Hosoi ◽  
Johji Inazawa ◽  
...  
Keyword(s):  
Cell Line ◽  
Embryonal Rhabdomyosarcoma ◽  
Over Expression ◽  
Myc Oncogene ◽  
Rhabdomyosarcoma Cell Line ◽  
Rhabdomyosarcoma Cell
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