A tight-binding model for MoS2 monolayers.

We propose an accurate tight-binding parametrization for the band structure of MoS2 monolayers near the main energy gap. We introduce a generic and straightforward derivation for the band energies equations that could be employed for other monolayer dichalcogenides. A parametrization that includes spin-orbit coupling is also provided. The proposed set of model parameters reproduce both the correct orbital compositions and location of valence and conductance band in comparison with ab initio calculations. The model gives a suitable starting point for realistic large-scale atomistic electronic transport calculations.

Inhibitory effect of HGF on invasiveness of aggressive MDA-MB231 breast carcinoma cells, and role of HDACs.

Hepatocyte growth factor (HGF), through Met receptor binding, fulfils numerous functions in invasive tumour growth (survival/proliferation, motility, apoptosis), but epigenetic control of gene expression in this process is poorly understood. In HGF-treated breast cancer cells we studied (a) the chemoinvasion towards CXCL12 (ligand of the chemokine-receptor CXCR4) and (b) the mechanistic basis, that is, the transduction pathways that regulate CXCR4-mediated invasion, and the role played by histone deacetylases (HDACs) after blockade with trichostatin A (TSA). In highly invasive and metastatic MDA-MB231 cells HGF had a dual inhibitory effect, reducing spontaneous migration and specific chemoinvasion towards CXCL12, the latter by decreasing CXCR4 transactivation and protein level. After HGF the levels of phosphorylated (therefore active) c-Src and Akt persistently increased, indicating a role of these signal transducers in the HGF-dependent cellular and molecular effects. c-Src wild-type expression vector (Srcwt) increased active c-Src and mimicked the HGF-dependent inhibition of CXCR4 transactivation. Our findings indicate that HDACs participated in the HGF-inhibitory effects. In fact, blockade of HDACs hindered the HGF- and Srcwt-dependent reductions of CXCR4 transactivation and invasiveness, while inhibition of endogenous c-Src was additive with HGF, further reducing specific chemoinvasion. In conclusion, in MDA-MB231 cells HDAC blockade with TSA partly counteracted the HGF-dependent effects through molecular events that included enhancement of the expression of the genes for invasiveness Met and CXCR4 (depending on serum conditions), reduction of endogenous phospho-c-Src/c-Src and phosphoAkt/Akt ratios and triggering of apoptosis. The potential therapeutic use of TSA should take into account the variable aggressiveness of breast carcinoma cells and microenvironment signals such as HGF at the secondary growth site of the tumour. It was interesting that HGF reduced motility and CXCR4 functionality only of MDA-MB231 cells, and not of low-invasive MCF-7 cells, suggesting a mechanism implicated in metastatic cell homing.

Hepatocyte growth factor differently influences Met-E-cadherin phosphorylation and downstream signaling pathway in two models of breast cells.

E-cadherins are implicated in cell adhesion, and also in cell signaling by associating with tyrosine kinase-receptors such as Met, the hepatocyte growth factor (HGF) receptor. Using two different cellular models, i.e. MCF-7 (breast carcinoma) and MCF-10 (immortalized mammary) cells, we studied the possible mechanism(s) by which E-cadherins modulate the signaling pathways downstream of Met, leading to beta-catenin-TCF transcriptional activity. In MCF-7, but not in MCF-10 cells, E-cadherins were remarkably associated with Met. Moreover, in MCF-7 cells both co-immunoprecipitation with anti-Met antibody and co-localization were increased by 30-min HGF treatment, which caused E-cadherin tyrosine phosphorylation. Also beta-catenin in the co-immunoprecipitate was phosphorylated by HGF, probably favoring TCF activation. Consistently, after HGF treatment, beta-catenin redistributed earlier in MCF-7 than in MCF-10 cells, with nuclear accumulation and activation of TOPFLASH gene reporter. Our results indicate a functional role of Met-E-cadherin interaction in MCF-7 cells through the amplification of the signaling downstream of HGF-Met triggering that involved c-Src and phosphoinositide-3-kinase activities.