Wallis, N;
Oberman, F;
Shurrush, K;
Germain, N;
Greenwald, G;
Gershon, T;
Pearl, T;
... Yisraeli, JK; + view all
(2021)
Small molecule inhibitor of Igf2bp1 represses Kras and a pro-oncogenic phenotype in cancer cells.
RNA Biology
pp. 1-18.
10.1080/15476286.2021.2010983.
(In press).
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Small molecule inhibitor of Igf2bp1 represses Kras and a pro oncogenic phenotype in cancer cells.pdf - Published Version Download (5MB) | Preview |
Abstract
Igf2bp1 is an oncofetal RNA binding protein whose expression in numerous types of cancers is associated with upregulation of key pro-oncogenic RNAs, poor prognosis, and reduced survival. Importantly, Igf2bp1 synergizes with mutations in Kras to enhance signalling and oncogenic activity, suggesting that molecules inhibiting Igf2bp1 could have therapeutic potential. Here, we isolate a small molecule that interacts with a hydrophobic surface at the boundary of Igf2bp1 KH3 and KH4 domains, and inhibits binding to Kras RNA. In cells, the compound reduces the level of Kras and other Igf2bp1 mRNA targets, lowers Kras protein, and inhibits downstream signalling, wound healing, and growth in soft agar, all in the absence of any toxicity. This work presents an avenue for improving the prognosis of Igf2bp1-expressing tumours in lung, and potentially other, cancer(s).
| Type: | Article |
|---|---|
| Title: | Small molecule inhibitor of Igf2bp1 represses Kras and a pro-oncogenic phenotype in cancer cells |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1080/15476286.2021.2010983 |
| Publisher version: | https://doi.org/10.1080/15476286.2021.2010983 |
| Language: | English |
| Additional information: | © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10140289 |
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