BEX2 suppresses mitochondrial activity and is required for dormant cancer stem cell maintenance in intrahepatic cholangiocarcinoma
| العنوان: | BEX2 suppresses mitochondrial activity and is required for dormant cancer stem cell maintenance in intrahepatic cholangiocarcinoma |
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| المؤلفون: | Jun Yasuda, Sadafumi Kawamura, Michiaki Unno, Yuta Wakui, Kennichi Satoh, Masamichi Mizuma, Ikuro Sato, Kazunori Yamaguchi, Mao Nakamura-Shima, Shin Ichiro Kanno, Mai Mochizuki, Akira Yasui, Koh Miura, Kuniharu Yamamoto, Kazuo Sugamura, Keiichi Tamai, Rie Shibuya-Takahashi, Makoto Abue, Wataru Iwai |
| المصدر: | Scientific Reports Scientific Reports, Vol 10, Iss 1, Pp 1-15 (2020) |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Science, USF2, Cell Cycle Proteins, Nerve Tissue Proteins, DNA-binding protein, Article, Cholangiocarcinoma, Gastrointestinal cancer, Oxygen Consumption, Cancer stem cell, Transcription (biology), Cell Line, Tumor, Medicine, Humans, Intrahepatic Cholangiocarcinoma, Cancer, Gene knockdown, Multidisciplinary, biology, business.industry, Cancer stem cells, medicine.disease, Cullin Proteins, Ubiquitin ligase, Mitochondria, Gene Expression Regulation, Neoplastic, Bile Duct Neoplasms, Cancer cell, biology.protein, Cancer research, Neoplastic Stem Cells, business, Carrier Proteins |
| الوصف: | 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 CD274low fraction of cholangiocarcinoma cells. Here we found that BEX2 was highly expressed in CD274low cells, and that BEX2 knockdown decreased the tumorigenicity and G0 phase of cholangiocarcinoma cells. BEX2 was found to be expressed predominantly in G0 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. Funding Statement: This research was supported in part by the Biomedical Research Core of Tohoku University Graduate School of Medicine. This research was supported in part by JSPS KAKENHI grant numbers JP: 19K08430, 17K10716, and 16K07132, and Practical Research for Innovative Cancer Control from AMED by grant number JP17ck0106197, The Cooperative Research Project Program of Joint Usage/Research Center at The Institute of Development, Aging and Cancer, Tohoku University, and Takeda Medical Foundation. Declaration of Interests: There are no financial conflicts of interest. Ethics Approval Statement: This study was conducted according to the principles expressed in the Declaration of Helsinki and was approved by the Ethics Committees at Miyagi Cancer Center (Natori, Japan) and Tohoku University Graduate School of Medicine (Sendai, Japan). The protocol of animal experiments was approved by the Miyagi Cancer Center Animal Care and Use Committee (permit number: MCC-AE-2019-8). |
| تدمد: | 2045-2322 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::eb5346553bf541640d21fd1fd236058a https://pubmed.ncbi.nlm.nih.gov/33299012 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....eb5346553bf541640d21fd1fd236058a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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