RRC ID 63612
Author Tamai K, Nakamura-Shima M, Shibuya-Takahashi R, Kanno SI, Yasui A, Mochizuki M, Iwai W, Wakui Y, Abue M, Yamamoto K, Miura K, Mizuma M, Unno M, Kawamura S, Sato I, Yasuda J, Yamaguchi K, Sugamura K, Satoh K.
Title BEX2 suppresses mitochondrial activity and is required for dormant cancer stem cell maintenance in intrahepatic cholangiocarcinoma.
Journal Sci Rep
Abstract 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.
Volume 10(1)
Pages 21592
Published 2020-12-9
DOI 10.1038/s41598-020-78539-0
PII 10.1038/s41598-020-78539-0
PMID 33299012
PMC PMC7725823
MeSH Bile Duct Neoplasms / genetics Bile Duct Neoplasms / metabolism* Bile Duct Neoplasms / pathology Carrier Proteins / genetics Carrier Proteins / metabolism Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism Cell Line, Tumor Cholangiocarcinoma / genetics Cholangiocarcinoma / metabolism* Cholangiocarcinoma / pathology Cullin Proteins / genetics Cullin Proteins / metabolism Gene Expression Regulation, Neoplastic* Humans Mitochondria / genetics Mitochondria / metabolism* Mitochondria / pathology Neoplastic Stem Cells / metabolism* Nerve Tissue Proteins / genetics Nerve Tissue Proteins / metabolism* Oxygen Consumption / physiology
IF 3.998
Human and Animal Cells HuCCT1(RCB1960) RBE(RCB1292) 293T(RCB2202)