TY - JOUR
T1 - EBNA1-targeted probe for the imaging and growth inhibition of tumours associated with the Epstein-Barr virus
AU - Jiang, Lijun
AU - Lan, Rongfeng
AU - Huang, Tao
AU - Chan, Chi-Fai
AU - Li, Hongguang
AU - Lear, Sam
AU - Zong, Jingyi
AU - Wong, Wing-Yan
AU - Muk-Lan Lee, Magnolia
AU - Dow Chan, Brandon
AU - Chan, Wai-Lun
AU - Lo, Wai-Sum
AU - Mak, Nai-Ki
AU - Li Lung, Maria
AU - Lok Lung, Hong
AU - Wah Tsao, Sai
AU - Taylor, Graham S.
AU - Bian, Zhao-Xiang
AU - Tai, William C. S.
AU - Law, Ga-Lai
AU - Wong, Wing-Tak
AU - Cobb, Steven L.
AU - Wong, Ka-Leung
N1 - Publication details (e.g. title, author(s), publication statuses and dates) are captured on an “AS IS” and “AS AVAILABLE” basis at the time of record harvesting from the data source. Suggestions for further amendments or supplementary information can be sent to [email protected].
PY - 2017/4/10
Y1 - 2017/4/10
N2 - Epstein-Barr nuclear antigen 1 (EBNA1), a dimeric oncoprotein of the Epstein-Barr virus (EBV), is essential for both viral-genome maintenance and the survival of infected cells. Despite EBNA1's potential as a therapeutic target, tools for the direct monitoring of EBNA1 in vitro and in vivo are lacking. Here, we show that a peptide-based inhibitor that luminesces when bound to EBNA1 inside the nucleus of EBV + cells can regulate EBNA1 homodimer formation and selectively inhibit the growth of EBV + tumours of nasopharyngeal carcinoma cells (C666-1 and NPC43) and Burkitt's lymphoma Raji cells. We also show that the peptide-based probe leads to 93% growth inhibition of EBV + tumours in mice. Our findings support the hypothesis that selective inhibition of EBNA1 dimerization can be used to afford better EBV-related cancer differentiation, and highlight the potential application of the probe as a new generation of biotracers for investigating the fundamental biological function of EBNA1 and for exploring its application as a therapeutic target. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
AB - Epstein-Barr nuclear antigen 1 (EBNA1), a dimeric oncoprotein of the Epstein-Barr virus (EBV), is essential for both viral-genome maintenance and the survival of infected cells. Despite EBNA1's potential as a therapeutic target, tools for the direct monitoring of EBNA1 in vitro and in vivo are lacking. Here, we show that a peptide-based inhibitor that luminesces when bound to EBNA1 inside the nucleus of EBV + cells can regulate EBNA1 homodimer formation and selectively inhibit the growth of EBV + tumours of nasopharyngeal carcinoma cells (C666-1 and NPC43) and Burkitt's lymphoma Raji cells. We also show that the peptide-based probe leads to 93% growth inhibition of EBV + tumours in mice. Our findings support the hypothesis that selective inhibition of EBNA1 dimerization can be used to afford better EBV-related cancer differentiation, and highlight the potential application of the probe as a new generation of biotracers for investigating the fundamental biological function of EBNA1 and for exploring its application as a therapeutic target. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
UR - https://www.scopus.com/pages/publications/85029945130
UR - https://www.scopus.com/pages/publications/85029945130#tab=impact
U2 - 10.1038/s41551-017-0042
DO - 10.1038/s41551-017-0042
M3 - RGC 21 - Publication in refereed journal
SN - 2157-846X
VL - 1
JO - Nature Biomedical Engineering
JF - Nature Biomedical Engineering
IS - 4
M1 - 0042
ER -
SDG 3 Good Health and Well-being