Induction of a SALL4-dependency for targeted cancer therapy
Nikki R. Kong,
Jianzhong Jeff Xi,
Leslie E. Silberstein,
Julie A.I. Thoms,
John E Pimanda,
Daniel G Tenen,
Posted 11 Jul 2020
bioRxiv DOI: 10.1101/2020.07.10.197434
Posted 11 Jul 2020
Oncofetal protein SALL4 is critical for tumor cell survival, making it a promising target in cancer therapy. However, it is detectable only in a subset of cancer patients, which limits the therapeutic impact of a SALL4 targeted therapy. Here we report that SALL4 can be activated and/or upregulated pharmacologically by hypomethylating agents, such as 5-Aza-2′-deoxycytidine (DAC), which are used clinically, and that SALL4 negative cancer cells become SALL4 dependent following exogenous expression of SALL4. In addition, the histone deacetylase inhibitor Entinostat (ENT) negatively regulates SALL4 expression by upregulating miR-205. Both ENT and miR-205 treatment induced cell apoptosis, rescuable by SALL4 expression or miR-205 inhibition. Finally, DAC pre-treatment sensitizes SALL4 negative cancer cell lines to ENT both in culture and in vivo by upregulating SALL4. Overall, we propose a framework whereby the scope of targeted therapy can be expanded by sensitizing cancer cells to treatment by target induction and engineered dependency. ### Competing Interest Statement The authors have declared no competing interest.
- Downloaded 124 times
- Download rankings, all-time:
- Site-wide: 116,993
- In cancer biology: 3,655
- Year to date:
- Site-wide: 80,116
- Since beginning of last month:
- Site-wide: 59,302
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!