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.
Highlights
Cancer stem cells (CSCs) define a subpopulation of cancer cells that are resistant to therapy
CD274-knockdown in cholangiocarcinoma cell lines resulted in increased tumorigenicity and aldehyde dehydrogenase (ALDH) activity, and CD274low cells are present in G 0 phase[6], suggesting that a C D274low fractions are enriched with dormant cancer stem cells
To investigate gene(s) responsible for dormant cancer stem cells enriched in the C D274low fraction of cholangiocarcinoma cells, we screened genes differentially expressed between CD274-knockdown and control RBE cholangiocarcinoma cells
Summary
Cancer stem cells (CSCs) define a subpopulation of cancer cells that are resistant to therapy. 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. CD274-knockdown in cholangiocarcinoma cell lines resulted in increased tumorigenicity and aldehyde dehydrogenase (ALDH) activity, and CD274low cells are present in G 0 phase[6], suggesting that a C D274low fractions are enriched with dormant cancer stem cells. The precise molecular mechanisms of how the CSC-phenotype is maintained are poorly understood in cholangiocarcinoma
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
