Scientific reports, 2020-12, Vol.10 (1), p.21592-21592, Article 21592
2020
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- Autor(en) / Beteiligte
- Titel
- BEX2 suppresses mitochondrial activity and is required for dormant cancer stem cell maintenance in intrahepatic cholangiocarcinoma
- Ist Teil von
- Scientific reports, 2020-12, Vol.10 (1), p.21592-21592, Article 21592
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2020
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Cancer stem cells (CSCs) define a subpopulation of cancer cells that are resistant to therapy. However, little is known of how CSC characteristics are regulated. We previously showed that dormant cancer stem cells are enriched with a CD274 fraction of cholangiocarcinoma cells. Here we found that BEX2 was highly expressed in CD274 cells, and that BEX2 knockdown decreased the tumorigenicity and G phase of cholangiocarcinoma cells. BEX2 was found to be expressed predominantly in G phase and starvation induced the USF2 transcriptional factor, which induced BEX2 transcription. Comprehensive screening of BEX2 binding proteins identified E3 ubiquitin ligase complex proteins, FEM1B and CUL2, and a mitochondrial protein TUFM, and further demonstrated that knockdown of BEX2 or TUFM increased mitochondria-related oxygen consumption and decreased tumorigenicity in cholangiocarcinoma cells. These results suggest that BEX2 is essential for maintaining dormant cancer stem cells through the suppression of mitochondrial activity in cholangiocarcinoma.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2045-2322eISSN: 2045-2322DOI: 10.1038/s41598-020-78539-0Titel-ID: cdi_doaj_primary_oai_doaj_org_article_46f507a261a544359c2ee01e6ca995c1
- Format
- –
- Schlagworte
- Bile Duct Neoplasms - genetics, Bile Duct Neoplasms - metabolism, Bile Duct Neoplasms - pathology, Cancer, Carrier Proteins - genetics, Carrier Proteins - metabolism, Cell Cycle Proteins - genetics, Cell Cycle Proteins - metabolism, Cell Line, Tumor, Cholangiocarcinoma, Cholangiocarcinoma - genetics, Cholangiocarcinoma - metabolism, Cholangiocarcinoma - pathology, Cullin Proteins - genetics, Cullin Proteins - metabolism, Gene Expression Regulation, Neoplastic, Humans, Mitochondria, Mitochondria - genetics, Mitochondria - metabolism, Mitochondria - pathology, Neoplastic Stem Cells - metabolism, Nerve Tissue Proteins - genetics, Nerve Tissue Proteins - metabolism, Oxygen consumption, Oxygen Consumption - physiology, Stem cells, Tumorigenicity, Ubiquitin, Ubiquitin-protein ligase