The endoplasmic reticulum (ER) stress occurs frequently in cancers. The unfolded protein response (UPR) is activated to cope with ER stress. This has generated widespread interest in targeting UPR as therapeutic strategies. Inositol-requiring transmembrane kinase/endonuclease 1α (IRE1α), an ER stress sensor, is a key component of UPR. However, the role of IRE1α in tumorigenesis remains unclear. The purpose of this work is to investigate the role of IRE1α in colon cancer and to determine whether IRE1α could serve as a target for therapy. We found that knockdown of IRE1α suppressed the proliferation of colon cancer cells in vitro and xenograft growth in vivo. Inhibition of expression of IRE1α decreased stemness of colon cancer stem cells (CSCs) and attenuated growth of intestinal organoids. Genetic ablation of IRE1α prevented the colitis-associated colonic tumorigenesis in mice. The mechanistic study indicates that knockdown of IRE1α repressed the expression of β-catenin, a key factor that drives colonic tumorigenesis, through activating pancreatic ER kinase/eukaryotic translation initiation factor 2α signaling. We found that the IRE1a-specific inhibitor 4μ8C could suppress the production of β-catenin, inhibited the proliferation of colon cancer cells, repressed colon CSCs and prevented xenograft growth. The results suggest that IRE1α has a critical role in colonic tumorigenesis and IRE1α targeting might be a strategy for treatment of colon cancers.
The optical properties of cubic GaN films have been investigated in the temperature range of 10–300 K. Five peaks were observed at 10 K. From the dependence of photoluminescence emissions on the temperature and excitation intensity, we have assigned two of the five peaks (2.926 and 2.821 eV) to donor–acceptor pair (DAP) transitions. Furthermore, these two peaks were found to be related to a common shallow donor involved in the peak position previously reported at 3.150 eV. The intensities of DAP transitions were much weaker than that of excitonic emission even at low temperature, indicating a relatively high purity of our samples.
Photoluminescence from a GaN0.015As0.985/GaAs quantum well has been measured at 15 K under hydrostatic pressure up to 9 GPa. Both the emissions from the GaNAs well and GaAs barrier are observed. The GaNAs-related peak shows a much weaker pressure dependence compared to that of the GaAs band gap. A group of new peaks appear in the spectra when the pressure is beyond 2.5 GPa, which is attributed to the emissions from the N isoelectronic traps in GaAs. The pressure dependence of the GaNAs-related peaks was calculated using the two-level model with the measured pressure coefficients of the GaAs band gap and N level as fitting parameters. It is found that the calculated results deviate seriously from the experimental data. An increasing of the emission intensity and the linewidth of the GaNAs-related peaks was also observed and briefly discussed.
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