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Cancer and Metastasis Reviews

Erschienen in:

14.04.2023

Oncogenic super-enhancers in cancer: mechanisms and therapeutic targets

verfasst von: Megan Bacabac, Wei Xu

Erschienen in: Cancer and Metastasis Reviews | Ausgabe 2/2023

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Abstract

Activation of oncogenes to sustain proliferative signaling and initiate metastasis are important hallmarks of cancer. Oncogenes are amplified or overexpressed in cancer cells and overexpression is often controlled at the level of transcription. Gene expression is tightly controlled by many cis-regulatory elements and trans-acting factors. Large clusters of enhancers known as “super-enhancers” drive robust expression of cell-fate determining transcription factors in cell identity. Cancer cells can take advantage of super-enhancers and become transcriptionally addicted to them leading to tumorigenesis and metastasis. Additionally, the cis-regulatory landscape of cancer includes aberrant super-enhancers that are not present in normal cells. The landscape of super-enhancers in cancer is characterized by high levels of histone H3K27 acetylation and bromodomain-containing protein 4 (BRD4), and Mediator complex. These chromatin features facilitate the identification of cancer type-specific and cell-type-specific super-enhancers that control the expression of important oncogenes to stimulate their growth. Disruption of super-enhancers via inhibiting BRD4 or other epigenetic proteins is a potential therapeutic option. Here, we will describe the discovery of super-enhancers and their unique characteristics compared to typical enhancers. Then, we will highlight how super-enhancer-associated genes contribute to cancer progression in different solid tumor types. Lastly, we will cover therapeutic targets and their epigenetic modulators.

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Titel: Oncogenic super-enhancers in cancer: mechanisms and therapeutic targets
verfasst von: Megan Bacabac
Wei Xu
Publikationsdatum: 14.04.2023
Verlag: Springer US
Erschienen in: Cancer and Metastasis Reviews / Ausgabe 2/2023
Print ISSN: 0167-7659
Elektronische ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-023-10103-4

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Oncogenic super-enhancers in cancer: mechanisms and therapeutic targets

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