LSD1 modulates the non-canonical integrin β3 signaling pathway in non-small cell lung carcinoma cells

The epigenetic writer lysine-specific demethylase 1 (LSD1) is aberrantly upregulated in many cancer types and its overexpression correlates with poor survival and tumor progression. In this study, we analysed LSD1 function in non-small cell lung cancer adenocarcinomas. Expression profiling of 182 cases of lung adenocarcinoma proved a significant correlation of LSD1 overexpression with lung adenocarcinoma progression and metastasis. KRAS-mutated lung cancer cell clones were stably silenced for LSD1 expression. RNA-seq and comprehensive pathway analysis revealed, that genes related to a recently described non-canonical integrin β3 pathway, were significantly downregulated by LSD1 silencing. Hence, invasion and self-renewal capabilities were strongly decreased. Notably, this novel defined LSD1/integrin β3 axis, was also detected in human lung adenocarcinoma specimens. Furthermore, the linkage of LSD1 to an altered expression pattern of lung-lineage specific transcription factors and genes, which are involved in alveolar epithelial differentiation, was demonstrated. Thus, our findings point to a LSD1-integrin β3 axis, conferring attributes of invasiveness and tumor progression to lung adenocarcinoma

Exclusive diffractive processes and the quark substructure of mesons

Exclusive diffractive processes on the nucleon are investigated within a model in which the quark-nucleon interaction is mediated by Pomeron exchange and the quark substructure of mesons is described within a framework based on the Dyson-Schwinger equations of QCD. The model quark-nucleon interaction has four parameters which are completely determined by high-energy $\pi N$ and $K N$ elastic scattering data. The model is then used to predict vector-meson electroproduction observables. The obtained $\rho$- and $\phi$-meson electroproduction cross sections are in excellent agreement with experimental data. The predicted $q^2$ dependence of $J/\psi$-meson electroproduction also agrees with experimental data. It is shown that confined-quark dynamics play a central role in determining the behavior of the diffractive, vector-meson electroproduction cross section. In particular, the onset of the asymptotic $1/q^4$ behavior of the cross section is determined by a momentum scale that is set by the current-quark masses of the quark and antiquark inside the vector meson. This is the origin of the striking differences between the $q^2$ dependence of $\rho$-, $\phi$- and $J/\psi$-meson electroproduction cross sections observed in recent experiments.Comment: 53 pages, 23 figures, revtex and epsfig. Minor additions to tex

Induction of antibacterial proteins and peptides in the coprophilous mushroom Coprinopsis cinerea in response to bacteria

Bacteria are the main nutritional competitors of saprophytic fungi during colonization of their ecological niches. This competition involves the mutual secretion of antimicrobials that kill or inhibit the growth of the competitor. Over the last years it has been demonstrated that fungi respond to the presence of bacteria with changes of their transcriptome, but the significance of these changes with respect to competition for nutrients is not clear as functional proof of the antibacterial activity of the induced gene products is often lacking. Here, we report the genome-wide transcriptional response of the coprophilous mushroom Coprinopsis cinerea to the bacteria Bacillus subtilis and Escherichia coli. The genes induced upon co-cultivation with each bacterium were highly overlapping, suggesting that the fungus uses a similar arsenal of effectors against Gram-positive and -negative bacteria. Intriguingly, the induced genes appeare to encode predominantly secreted peptides and proteins with predicted antibacterial activities, which was validated by comparative proteomics of the C. cinerea secretome. Induced members of two putative antibacterial peptide and protein families in C. cinerea, the cysteine-stabilized αβ-defensins (Csαβ-defensins) and the GH24-type lysozymes, were purified, and their antibacterial activity was confirmed. These results provide compelling evidence that fungi are able to recognize the presence of bacteria and respond with the expression of an arsenal of secreted antibacterial peptides and proteins