Extracellular ATP promotes angiogenesis and adhesion of TNBC cells to endothelial cells via upregulation of CTGF.

Our previous works have indicated that extracellular ATP is an important prometastasis factor. However, the molecular mechanism involved needs to be further studied. We demonstrated that extracellular ATP treatment could upregulate the expression of connective tissue growth factor (CTGF) in both triple-negative breast cancer (TNBC) cells and endothelial cells (ECs). Extracellular ATP stimulated the migration of TNBC cells and ECs, and angiogenesis of ECs via the P2Y2--YAP-CTGF axis. Furthermore, we demonstrated that adenosine triphosphate (ATP) stimulated TNBC cell adhesion to ECs and transmigration through the EC layer via CTGF by upregulation of integrin ß1 on TNBC cells and VCAM-1 on ECs. Both apyrase (ATP-diphosphohydrolase) and CTGF shRNA treatments could inhibit the metastasis of inoculated tumors to lung and liver in a mouse model, and these treated tumors had fewer blood vessels. Collectively, our data indicated that extracellular ATP promotes tumor angiogenesis and the interactions between TNBC cells and ECs through upregulation of CTGF, thereby stimulating TNBC metastasis. The pleiotropic effects of ATP in angiogenesis and cell adhesion suggest that extracellular ATP or CTGF could be an effective target for TNBC therapy.

The risk variant rs11836367 contributes to breast cancer onset and metastasis by attenuating Wnt signaling via regulating NTN4 expression.

Most genome-wide association study (GWAS)-identified breast cancer-associated causal variants remain uncharacterized. To provide a framework of understanding GWAS-identified variants to function, we performed a comprehensive study of noncoding regulatory variants at the NTN4 locus (12q22) and NTN4 gene in breast cancer etiology. We find that rs11836367 is the more likely causal variant, disrupting enhancer activity in both enhancer reporter assays and endogenous genome editing experiments. The protective T allele of rs11837367 increases the binding of GATA3 to the distal enhancer and up-regulates NTN4 expression. In addition, we demonstrate that loss of NTN4 gene in mice leads to tumor earlier onset, progression, and metastasis. We discover that NTN4, as a tumor suppressor, can attenuate the Wnt signaling pathway by directly binding to Wnt ligands. Our findings bridge the gaps among breast cancer-associated single-nucleotide polymorphisms, transcriptional regulation of NTN4, and breast cancer biology, which provides previously unidentified insights into breast cancer prediction and prevention.

[Mechanisms of Fe-cyclam/H2O2 System Catalyzing the Degradation of Rhodamine B].

Fenton reaction is a traditional method for the treatment of dye-containing wastewater. However, this process should be performed in a narrow pH range and requires large amounts of ferrous salt input, limiting its application. In this work, a robust iron complex bearing a cross-bridge cyclam ligand (Fe-cyclam) was successfully prepared. This complex could effectively activate H2O2 to degrade rhodamine B at a pH range of 2-7. The Fe-cyclam/H2O2 system was more effective in the degradation of rhodamine B than the Fenton reaction, when the input [Fe] was lower than 50 µmol·L-1. Moreover, in addition to rhodamine B, the Fe-cyclam/H2O2 system was also capable of degrading dyes such as acid red 88, acid orange II, reactive red 24, and neutral red. This system was more efficient in the degradation of azo dyes than that of triphenylmethane dyes. The removal of rhodamine B remained higher than 90% in three cycle experiments, indicating the excellent stability of Fe-cyclam. The quenching experiments proved that the degradation of rhodamine B by Fe-cyclam/H2O2 was a free-radical-control process. Meanwhile, the electron paramagnetic resonance captured the signals of high valent FeV-oxo species, indicating that FeV-oxo possibly mediated the degradation of rhodamine B in the Fe-cyclam/H2O2 system. This work proves the potential application of Fe-cyclam/H2O2 in the degradation of dyes in a practical environment.

Light-driven nitrous oxide production via autotrophic denitrification by self-photosensitized Thiobacillus denitrificans.

N2O (Nitrous oxide, a booster oxidant in rockets) has attracted increasing interest as a means of enhancing energy production, and it can be produced by nitrate (NO3-) reduction in NO3--loading wastewater. However, conventional denitrification processes are often limited by the lack of bioavailable electron donors. In this study, we innovatively propose a self-photosensitized nonphototrophic Thiobacillus denitrificans (T. denitrificans-CdS) that is capable of NO3- reduction and N2O production driven by light. The system converted >72.1 ±â€¯1.1% of the NO3--N input to N2ON, and the ratio of N2O-N in gaseous products was >96.4 ±â€¯0.4%. The relative transcript abundance of the genes encoding the denitrifying proteins in T. denitrificans-CdS after irradiation was significantly upregulated. The photoexcited electrons acted as the dominant electron sources for NO3- reduction by T. denitrificans-CdS. This study provides the first proof of concept for sustainable and low-cost autotrophic denitrification to generate N2O driven by light. The findings also have strong implications for sustainable environmental management because the sunlight-triggered denitrification reaction driven by nonphototrophic microorganisms may widely occur in nature, particularly in a semiconductive mineral-enriched aqueous environment.