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ALKBH overexpression in head and neck cancer: potential target for novel anticancer therapy

Pilżys, Tomasz and Marcinkowski, Michał and Kukwa, Wojciech and Garbicz, Damian and Dylewska, Małgorzata and Ferenc, Karolina and Mieczkowski, Adam and Kukwa, Wojciech and Migacz, Ewa and Wołosz, Dominika and Mielecki, Damian and Klungland, Arne and Piwowarski, Jan and Poznański, Jarosław and Grzesiuk, Elzbieta (2019) ALKBH overexpression in head and neck cancer: potential target for novel anticancer therapy. Scientific Reports, 9 (1). p. 13249. ISSN 2045-2322

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Official URL: https://www.nature.com/articles/s41598-019-49550-x

Abstract

The nine identified human homologues of E. coli AlkB 2-oxoglutarate (2OG) and Fe(II)-dependent dioxygenase, ALKBH1-8 and FTO, display different substrate specificities and diverse biological functions. Here we discovered the combined overexpression of members of the ALKBH family in head and neck squamous cell carcinomas (HNSCC). We found direct correlation of ALKBH3 and FTO expression with primary HNSCC tumor size. We observed unidentified thus far cytoplasmic localization of ALKBH2 and 5 in HNSCC, suggesting abnormal role(s) of ALKBH proteins in cancer. Further, high expression of ALKBHs was observed not only in HNSCC, but also in several cancerous cell lines and silencing ALKBH expression in HeLa cancer cells resulted in dramatically decreased survival. considering the discovered impact of high expression of ALKBH proteins on HNSCC development, we screened for ALKBH blockers among newly synthetized anthraquinone derivatives and demonstrated their potential to support standard anticancer therapy.

Item Type:Article
Subjects:R Medicine > R Medicine (General)
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
R Medicine > RM Therapeutics. Pharmacology
Divisions:Department of Molecular Biology
ID Code:1756
Deposited By: Prof. Elżbieta Grzesiuk
Deposited On:09 Oct 2019 08:08
Last Modified:09 Oct 2019 08:08

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