Imperial College London
Alternate

DrNeloferSyed

Faculty of Medicine, Department of Brain Sciences

Senior Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 5292n.syed

 
 
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Location

 

E506Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Atkinson:2019:10.1016/j.jid.2018.10.038,
author = {Atkinson, A and Renziehausen, A and Wang, H and Lo, Nigro C and Lattanzio, L and Merlano, M and Rao, B and Weir, L and Evans, A and Matin, R and Harwood, C and Szlosarek, P and Pickering, JG and Fleming, C and Sim, VR and Li, S and Vasta, JT and Raines, RT and Boniol, M and Thompson, A and Proby, C and Crook, T and Syed, N},
doi = {10.1016/j.jid.2018.10.038},
journal = {Journal of Investigative Dermatology},
pages = {1118--1126},
title = {The collagen prolyl hydroxylases are bifunctional growth regulators in melanoma},
url = {http://dx.doi.org/10.1016/j.jid.2018.10.038},
volume = {139},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Appropriate post-translational processing of collagen requires prolyl hydroxylation, catalyzed by the prolyl 3- (C-P3H) and prolyl 4- (C-P4H) hydroxylases is essential for normal cell function. Here we have investigated the expression, transcriptional regulation and function of the C-P3H and C-P4H families in melanoma. We show that the CP3H family exemplified by Leprel1 and Leprel2 are subject to methylation-dependent transcriptional silencing in primary and metastatic melanoma consistent with a tumour suppressor function. In contrast, although there is transcriptional silencing of P4HA3 in a sub-set of melanomas, the CP4H family members P4HA1, P4HA2 and P4HA3 are often over-expressed in melanoma, expression being prognostic of worse clinical outcomes. Consistent with tumour suppressor function, ectopic expression of Leprel1 and Leprel2 inhibits melanoma proliferation, whereas P4HA2 and P4HA3 increase proliferation and particularly invasiveness of melanoma cells. Pharmacological inhibition with multiple selective C-P4H inhibitors reduces proliferation and inhibits invasiveness of melanoma cells. Together, our data identify the C-P3H and C-P4H families as potentially important regulators of melanoma growth and invasiveness and suggest that selective inhibition of C-P4H is an attractive strategy to reduce the invasive properties of melanoma cells.
AU  - Atkinson,A
AU  - Renziehausen,A
AU  - Wang,H
AU  - Lo,Nigro C
AU  - Lattanzio,L
AU  - Merlano,M
AU  - Rao,B
AU  - Weir,L
AU  - Evans,A
AU  - Matin,R
AU  - Harwood,C
AU  - Szlosarek,P
AU  - Pickering,JG
AU  - Fleming,C
AU  - Sim,VR
AU  - Li,S
AU  - Vasta,JT
AU  - Raines,RT
AU  - Boniol,M
AU  - Thompson,A
AU  - Proby,C
AU  - Crook,T
AU  - Syed,N
DO  - 10.1016/j.jid.2018.10.038
EP  - 1126
PY  - 2019///
SN  - 0022-202X
SP  - 1118
TI  - The collagen prolyl hydroxylases are bifunctional growth regulators in melanoma
T2  - Journal of Investigative Dermatology
UR  - http://dx.doi.org/10.1016/j.jid.2018.10.038
UR  - https://www.ncbi.nlm.nih.gov/pubmed/30452903
UR  - https://www.sciencedirect.com/science/article/pii/S0022202X18328227?via%3Dihub
UR  - http://hdl.handle.net/10044/1/65729
VL  - 139
ER  -
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