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

2020 ◽  
Author(s):  
Ananya Pal ◽  
Jia Yu Leung ◽  
Gareth Chin Khye Ang ◽  
Vinay Kumar Rao ◽  
Luca Pignata ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Embryonal Rhabdomyosarcoma ◽  
Author Response ◽  
Potential Target

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.

scholarly journals Author response: Ubiquitin-dependent folding of the Wnt signaling coreceptor LRP6

2016 ◽  
Author(s):  
Elsa Perrody ◽  
Laurence Abrami ◽  
Michal Feldman ◽  
Beatrice Kunz ◽  
Sylvie Urbé ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Author Response

scholarly journals Impaired Wnt Signaling in Embryonal Rhabdomyosarcoma Cells from p53/c-fos Double Mutant Mice

2010 ◽  
Vol 177 (4) ◽  
pp. 2055-2066 ◽  
Author(s):  
Shalini Singh ◽  
Charles Vinson ◽  
Cathy M. Gurley ◽  
Greg T. Nolen ◽  
Marjorie L. Beggs ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Double Mutant ◽  
Embryonal Rhabdomyosarcoma ◽  
Mutant Mice

scholarly journals Deregulation of the histone H3K9 di-methylation landscape suppresses canonical Wnt signaling in embryonal rhabdomyosarcoma

2020 ◽  
Author(s):  
Ananya Pal ◽  
Jia Yu Leung ◽  
Gareth Chin Khye Ang ◽  
Vinay Kumar Rao ◽  
Luca Pignata ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Myogenic Differentiation ◽  
Wnt Signaling Pathway ◽  
Embryonal Rhabdomyosarcoma ◽  
Dependent Manner ◽  
Canonical Wnt Signaling ◽  
Therapeutic Modalities ◽  
Canonical Wnt

AbstractThe Wnt signaling pathway is down-regulated in embryonal rhabdomyosarcoma (ERMS) and contributes to the block of myogenic differentiation. Epigenetic mechanisms leading to its suppression are unknown and could pave the way towards novel therapeutic modalities. In this study, we demonstrate that the H3K9 lysine methyltransferase G9a suppresses canonical Wnt signaling by activating expression of the Wnt antagonist DKK1. Inhibition of G9a expression or activity reduced DKK1 expression and elevated canonical Wnt signaling resulting in myogenic differentiation in vitro and in vivo. Mechanistically, G9a impacted Sp1 and p300 enrichment at the DKK1 promoter in a methylation-dependent manner. The reduced tumor growth upon G9a deficiency was reversed by recombinant DKK1 or LGK974, which also inhibits Wnt signaling. Consistently, among thirteen drugs targeting chromatin modifiers, G9a inhibitors were highly effective in reducing ERMS cell viability. Together, our study demonstrates that ERMS cells are vulnerable to G9a inhibitors and suggest that targeting the G9a-DKK1-β-catenin node holds promise for differentiation therapy.

scholarly journals Author response: Light-activated Frizzled7 reveals a permissive role of non-canonical wnt signaling in mesendoderm cell migration

2018 ◽  
Author(s):  
Daniel Čapek ◽  
Michael Smutny ◽  
Alexandra-Madelaine Tichy ◽  
Maurizio Morri ◽  
Harald Janovjak ◽  
...  
Keyword(s):  
Cell Migration ◽  
Wnt Signaling ◽  
Author Response ◽  
Canonical Wnt Signaling ◽  
Response Light ◽  
Canonical Wnt ◽  
Permissive Role
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