Zezhi Shan

In this study, a kind of graphene oxide-cuprous oxide (GO-Cu 2 O) nanocomposites was fabricated with different morphologies to serve as a photocatalytic material for the degradation of organic/inorganic dyes under visible light and the bactericidal effect against pathogenic bacteria. The GO-Cu 2 O was prepared with solid cube and hollow dodecahedra morphologies through in-situ synthesis, and characterized by scanning electron microscopy (SEM), transmission electron microscope (TEM), X-ray diffraction (XRD), Raman, Ultraviolet and visible spectrophotometry (UV/vis), and Fourier transform infrared spectroscopy. In comparison with cubic GO-Cu 2 O, the absorption and degradation efficiency of the GO-Cu 2 O dodecahedra (GCD) composite in Methyl orange (MO), Rhodamine B (RhB), and phenol was higher owning to the more active sites for the simultaneous dye and light absorption of hollow structure. The antibacterial effect of the GO-Cu2O dodecahedra was examined by the flat colony counting method with an excellent bactericidal effect against pathogenic bacteria. The possible mechanism for the preparation of GCD possessing the enhancement of the visible-light photocatalytic and antibacterial efficiencies were also investigated.

Abstract Ferroptosis is a lipid peroxidation-dependent cell death caused by metabolic dysfunction. Ferroptosis-associated enzymes are promising therapeutic targets for cancer treatment. However, such therapeutic strategies show limited efficacy due to drug resistance and other largely unknown underlying mechanisms. Here we report that cystine transporter SLC7A11 is upregulated in lung cancer stem-like cells (CSLC) and can be activated by stem cell transcriptional factor SOX2. Mutation of SOX2 binding site in SLC7A11 promoter reduced SLC7A11 expression and increased sensitivity to ferroptosis in cancer cells. Oxidation at Cys265 of SOX2 inhibited its activity and decreased the self-renewal capacity of CSLCs. Moreover, tumors with high SOX2 expression were more resistant to ferroptosis, and SLC7A11 expression was positively correlated with SOX2 in both mouse and human lung cancer tissue. Together, our study provides a mechanism by which cancer cells evade ferroptosis and suggests that oxidation of SOX2 can be a potential therapeutic target for cancer treatment. Significance: This study uncovers a SOX2–SLC7A11 regulatory axis that confers resistance to ferroptosis in lung cancer stem-like cells.

Cyclic GMP-AMP synthase (cGAS) is the major sensor for cytosolic DNA and activates type I interferon signaling and plays an essential role in antitumor immunity. However, it remains unclear whether the cGAS-mediated antitumor activity is affected by nutrient status. Here, our study reports that methionine deprivation enhances cGAS activity by blocking its methylation, which is catalyzed by methyltransferase SUV39H1. We further show that methylation enhances the chromatin sequestration of cGAS in a UHRF1-dependent manner. Blocking cGAS methylation enhances cGAS-mediated antitumor immunity and suppresses colorectal tumorigenesis. Clinically, cGAS methylation in human cancers correlates with poor prognosis. Thus, our results indicate that nutrient stress promotes cGAS activation via reversible methylation, and suggest a potential therapeutic strategy for targeting cGAS methylation in cancer treatment.

Recent studies have indicated that the epithelial-mesenchymal transition (EMT) is a key molecular mechanism involved in the development of colorectal cancer (CRC). N-cadherin is a mesenchymal marker of the EMT and has been closely linked to several human malignancies. However, its role in CRC has remained elusive. In the present study, qRT-PCR and western blot analysis indicated that N-cadherin expression was higher in tumor tissues than in that in their adjacent normal tissues. Immunohistochemical evaluation of N-cadherin and E-cadherin (an epithelial marker of the EMT), indicated that N-cadherin expression was significantly associated with tumor differentiation, tumor size as well as tumor, nodes and metastasis stage. Correlation analysis suggested the expression of N-cadherin was negatively correlated with that of E-cadherin in CRC tissues. Kaplan-Meier analysis indicated that patients with high N-cadherin expression had a significantly lower overall survival and disease-free survival rate than those with low N-cadherin expression, while the opposite was found for E-cadherin. Of note, the present study found that high N-cadherin expression was an independent prognostic factor for CRC. In vitro assays showed that N-cadherin was widely expressed in CRC cell lines and silencing of N-cadherin suppressed the proliferation and migration of the CRC cell line HT-29 by upregulating E-cadherin, suggesting a potential role of N-cadherin in inducing EMT. In conclusion, the present study suggested that N-cadherin has the potential of serving as a novel prognostic predictor and a promising therapeutic target for CRC.