Imperial College London
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ProfessorHectorKeun

Faculty of Medicine, Department of Surgery & Cancer

Professor of Biochemistry
 
 
 
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Contact

 

+44 (0)20 7594 3161h.keun

 
 
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Location

 

officesInstitute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Garcia-Dominguez:2022:10.1038/s41388-022-02279-w,
author = {Garcia-Dominguez, DJ and Hajji, N and Lopez-Alemany, R and Sanchez-Molina, S and Figuerola-Bou, E and Civanto, FJM and Rello-Varona, S and Andres-Leon, E and Benito, A and Keun, HC and Mora, J and Tirado, OM and de, Alava E and Hontecillas-Prieto, L},
doi = {10.1038/s41388-022-02279-w},
journal = {Oncogene},
pages = {2638--2650},
title = {Selective histone methyltransferase G9a inhibition reduces metastatic development of Ewing sarcoma through the epigenetic regulation of NEU1},
url = {http://dx.doi.org/10.1038/s41388-022-02279-w},
volume = {41},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Ewing sarcoma (EWS) is an aggressive bone and soft tissue tumor with high susceptibility to metastasize. The underlying molecular mechanisms leading to EWS metastases remain poorly understood. Epigenetic changes have been implicated in EWS tumor growth and progression. Linking epigenetics and metastases may provide insight into novel molecular targets in EWS and improve its treatment. Here, we evaluated the effects of a selective G9a histone methyltransferase inhibitor (BIX01294) on EWS metastatic process. Our results showed that overexpression of G9a in tumors from EWS patients correlates with poor prognosis. Moreover, we observe a significantly higher expression of G9a in metastatic EWS tumor as compared to either primary or recurrent tumor. Using functional assays, we demonstrate that pharmacological G9a inhibition using BIX01294 disrupts several metastatic steps in vitro, such as migration, invasion, adhesion, colony formation and vasculogenic mimicry. Moreover, BIX01294 reduces tumor growth and metastases in two spontaneous metastases mouse models. We further identified the sialidase NEU1 as a direct target and effector of G9a in the metastatic process in EWS. NEU1 overexpression impairs migration, invasion and clonogenic capacity of EWS cell lines. Overall, G9a inhibition impairs metastases in vitro and in vivo through the overexpression of NEU1. G9a has strong potential as a prognostic marker and may be a promising therapeutic target for EWS patients.
AU  - Garcia-Dominguez,DJ
AU  - Hajji,N
AU  - Lopez-Alemany,R
AU  - Sanchez-Molina,S
AU  - Figuerola-Bou,E
AU  - Civanto,FJM
AU  - Rello-Varona,S
AU  - Andres-Leon,E
AU  - Benito,A
AU  - Keun,HC
AU  - Mora,J
AU  - Tirado,OM
AU  - de,Alava E
AU  - Hontecillas-Prieto,L
DO  - 10.1038/s41388-022-02279-w
EP  - 2650
PY  - 2022///
SN  - 0950-9232
SP  - 2638
TI  - Selective histone methyltransferase G9a inhibition reduces metastatic development of Ewing sarcoma through the epigenetic regulation of NEU1
T2  - Oncogene
UR  - http://dx.doi.org/10.1038/s41388-022-02279-w
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000775854600001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.nature.com/articles/s41388-022-02279-w
UR  - http://hdl.handle.net/10044/1/97469
VL  - 41
ER  -
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