Abstract
Abstract Osteosarcoma (OS) is the most common primary malignant bone tumor in oncopediatrics. Despite therapeutic advances, the 5-year survival rate is 30% in bad responders to treatment or when pulmonary metastases are present at diagnosis. It is therefore urgent to better understand the molecular mechanisms involved in the development of OS in order to identify new therapeutic targets. As a major player in the stress response, it has recently been shown that the transcription factor HSF1 coordonates a stress-independent transcriptional program involving it in many pro-tumor biological processes in different cancers. A better understanding of the mechanisms by which HSF1 activity participates in tumor development is therefore essential to consider its therapeutic targeting. The co-partners of HSF1 to DNA, by modulating its transcriptional activity, could explain its pleiotropic effects. Based on this hypothesis, TRIM33 was identified by RIME. TRIM33 is known as a transcriptional cofactor and its involvement in various cancers. In this context, our objective is to study the interaction between TRIM33 and HSF1, their common genomic localization and to investigate the involvement of TRIM33 in the development of OS. Our results show that TRIM33 and HSF1 co-localize in the nucleus in OS TMA and by immuno-fluorescence in tumor cells and preclinical models. Furthermore, we observed by chIP-seq that TRIM33 and HSF1 share common DNA binding sites. Finally, our preliminary results show that TRIM33 invalidation by RNA interference in OS cell lines decreases tumor cell proliferation. Thus, in view of its role as a DNA partner of HSF1, TRIM33 is an interesting therapeutic target in OS. This work was supported by la Fédération Enfants et Santé, la SFCE et La ligue Contre le Cancer (comités 44, 49) Citation Format: Morgane Lallier, Robel Tefaye, Brice Moukengué, Céline Charrier, Rose-Anne Thepault, Benedicte Brounais-Le Royer, Marc Baud'huin, Franck Verrecchia, Benjamin Ory, François Lamoureux. TRIM33 interacts with HSF1 in osteosarcoma development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3902.
Published Version
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