RNF40 epigenetically modulates glycolysis to support the aggressiveness of 
basal-like breast cancer

Prokakis, Evangelos; Jansari, Shaishavi; Boshnakovska, Angela; Wiese, Maria; Kusch, Kathrin; Kramm, Christof; Dullin, Christian; Rehling, Peter; Glatzel, Markus; Pantel, Klaus; Wikman, Harriet; Johnsen, Steven A.; Gallwas, Julia; Wegwitz, Florian

doi:10.1038/s41419-023-06157-5

アイテム詳細

登録内容を編集ファイル形式で保存

一時保存へ追加

タグ情報を表示リリース履歴を表示詳細要約

公開

学術論文

RNF40 epigenetically modulates glycolysis to support the aggressiveness of basal-like breast cancer

MPS-Authors

/persons/resource/persons221404

Dullin, Christian
Research Group of Translational Molecular Imaging, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society;

External Resource

There are no locators available

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

フルテキスト (公開)

s41419-023-06157-5.pdf
(出版社版), 8MB

付随資料 (公開)

There is no public supplementary material available

引用

Prokakis, E., Jansari, S., Boshnakovska, A., Wiese, M., Kusch, K., Kramm, C., Dullin, C., Rehling, P., Glatzel, M., Pantel, K., Wikman, H., Johnsen, S. A., Gallwas, J., & Wegwitz, F. (2023). RNF40 epigenetically modulates glycolysis to support the aggressiveness of basal-like breast cancer. Cell Death and Disease, 14(9):. doi:10.1038/s41419-023-06157-5.

引用: https://hdl.handle.net/21.11116/0000-000E-293F-F

要旨

Triple-negative breast cancer (TNBC) is the most difficult breast cancer subtype to treat due to the lack of targeted therapies. Cancer stem cells (CSCs) are strongly enriched in TNBC lesions and are responsible for the rapid development of chemotherapy resistance and metastasis. Ubiquitin-based epigenetic circuits are heavily exploited by CSCs to regulate gene transcription and ultimately sustain their aggressive behavior. Therefore, therapeutic targeting of these ubiquitin-driven dependencies may reprogram the transcription of CSC and render them more sensitive to standard therapies. In this work, we identified the Ring Finger Protein 40 (RNF40) monoubiquitinating histone 2B at lysine 120 (H2Bub1) as an indispensable E3 ligase for sustaining the stem-cell-like features of the growing mammary gland. In addition, we found that the RNF40/H2Bub1-axis promotes the CSC properties and drug-tolerant state by supporting the glycolytic program and promoting pro-tumorigenic YAP1-signaling in TNBC. Collectively, this study unveils a novel tumor-supportive role of RNF40 and underpins its high therapeutic value to combat the malignant behavior of TNBC.