Imperial College London
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Professor Hani Gabra

Faculty of Medicine, Department of Surgery & Cancer

Emeritus Professor of Medical Oncology
 
 
 
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Contact

 

h.gabra Website

 
 
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Assistant

 

Ms Sophie Lions +44 (0)20 7594 2792

 
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Location

 

Garry Weston CentreCancer CentreHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Birtley:2019:10.1038/s41467-019-10966-8,
author = {Birtley, JR and Alomary, M and Zanini, E and Antony, J and Maben, Z and Weaver, G and von, Arx C and Mura, M and Marinho, AT and Lu, H and Morecroft, E and Karali, E and Chayen, N and Tate, E and Jurewicz, M and Stern, L and Recchi, C and Gabra, H},
doi = {10.1038/s41467-019-10966-8},
journal = {Nature Communications},
title = {Inactivating mutations and X-ray crystal structure of the tumor suppressor OPCML reveal cancer-associated functions},
url = {http://dx.doi.org/10.1038/s41467-019-10966-8},
volume = {10},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - OPCML, a tumor suppressor gene, is frequently silenced epigenetically in ovarian and other cancers. Here we report, by analysis of databases of tumor sequences, the observation of OPCML somatic missense mutations from various tumor types and the impact of these mutations on OPCML function, by solving the X-ray crystal structure of this glycoprotein to 2.65 Å resolution. OPCML consists of an extended arrangement of three immunoglobulin-like domains and homodimerizes via a network of contacts between membrane-distal domains. We report the generation of a panel of OPCML variants with representative clinical mutations and demonstrate clear phenotypic effects in vitro and in vivo including changes to anchorage-independent growth, interaction with activated cognate receptor tyrosine kinases, cellular migration, invasion in vitro and tumor growth in vivo. Our results suggest that clinically occurring somatic missense mutations in OPCML have the potential to contribute to tumorigenesis in a variety of cancers.
AU  - Birtley,JR
AU  - Alomary,M
AU  - Zanini,E
AU  - Antony,J
AU  - Maben,Z
AU  - Weaver,G
AU  - von,Arx C
AU  - Mura,M
AU  - Marinho,AT
AU  - Lu,H
AU  - Morecroft,E
AU  - Karali,E
AU  - Chayen,N
AU  - Tate,E
AU  - Jurewicz,M
AU  - Stern,L
AU  - Recchi,C
AU  - Gabra,H
DO  - 10.1038/s41467-019-10966-8
PY  - 2019///
SN  - 2041-1723
TI  - Inactivating mutations and X-ray crystal structure of the tumor suppressor OPCML reveal cancer-associated functions
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/s41467-019-10966-8
UR  - http://hdl.handle.net/10044/1/71553
VL  - 10
ER  -
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