Mst Out and HCC In

Mst1 and Mst2 are key components of the Hippo tumor suppressor pathway. In this issue, Zhou et al. (2009) reported that Mst1/2 ablation leads to hepatocellular carcinomas. Unexpectedly, Mst1/2 may activate another kinase besides Lats1 and Lats2 to phosphorylate YAP, and the role of Mst1/2 in YAP regulation is cell type dependent

MicroRNA-143 Targets MACC1 to Inhibit Cell Invasion and Migration in Colorectal cancer

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) have been suggested to play a vital role in tumor initiation and progression by negatively regulating oncogenes and tumor suppressors. Quite recently, studies have identified some miRNAs operating to promote or suppress tumor invasion or metastasis via regulating metastasis-related genes, providing potential therapeutic targets on anti-metastasis strategy. Metastasis-associated in colon cancer-1 (MACC1) has been newly identified to express highly in colorectal cancer (CRC) and promote tumor metastasis through transactivating metastasis-inducing HGF/MET signaling pathway. In this study, we investigated whether miRNA 143 is involved in the regulation of MACC1 and thus plays a functional role in CRC.</p> <p>Results</p> <p>Using both in silico prediction and western blot assay, we found the previously reported tumor suppressive miR-143 targeted MACC1 in CRC. The direct interaction between them was confirmed by 3' UTR luciferase reporter gene. In concordance with the inhibitory effects induced by siRNA mediated knockdown of MACC1, restoration of miR-143 by mimics in SW620 cells significantly attenuated cell growth, migration and invasion. It is notable that combined treatment of miR-143 mimics and MACC1 siRNA induced synergistic inhibitory effects compared to either miR-143 mimics or MACC1 siRNA treatment alone. Conversely, reduction of miR-143 by inhibitors in SW480 cells apparently stimulated these phenotypes. Furthermore, we observed that miR-143 level was inversely correlated with MACC1 mRNA expression in CRC tissues.</p> <p>Conclusions</p> <p>Our findings newly described miR-143/MACC1 link and provided a potential mechanism for MACC1 dysregulation and contribution to CRC cell invasion. It may help to estimate the therapeutic utility of miR-143 in CRC.</p

Large-scale Huygens metasurfaces for holographic 3D near-eye displays

Novel display technologies aim at providing the users with increasingly immersive experiences. In this regard, it is a long-sought dream to generate three-dimensional (3D) scenes with high resolution and continuous depth, which can be overlaid with the real world. Current attempts to do so, however, fail in providing either truly 3D information, or a large viewing area and angle, strongly limiting the user immersion. Here, we report a proof-of-concept solution for this problem, and realize a compact holographic 3D near-eye display with a large exit pupil of 10mm x 8.66mm. The 3D image is generated from a highly transparent Huygens metasurface hologram with large (>10^8) pixel count and subwavelength pixels, fabricated via deep-ultraviolet immersion photolithography on 300 mm glass wafers. We experimentally demonstrate high quality virtual 3D scenes with ~50k active data points and continuous depth ranging from 0.5m to 2m, overlaid with the real world and easily viewed by naked eye. To do so, we introduce a new design method for holographic near-eye displays that, inherently, is able to provide both parallax and accommodation cues, fundamentally solving the vergence-accommodation conflict that exists in current commercial 3D displays.Comment: 21 pages, 9 figure

Tumour suppressor SIRT3 deacetylates and activates manganese superoxide dismutase to scavenge ROS

Tumour suppressor SIRT3 deacetylates and activates manganese superoxide dismutase to scavenge ROSMitochondria manganese superoxide dismutase (SOD2) is a major antioxidant enzyme associated with several diseases. This study shows that SOD2 is inhibited by acetylation and activated by SIRT3-mediated deacetylation in response to reactive oxygen species (ROS).Mitochondria manganese superoxide dismutase (SOD2) is an important antioxidant enzyme, deficiency of which is associated with various human diseases. The known primary regulation of SOD2 is through transcriptional activation. Here, we report that SOD2 is acetylated at Lys 68 and that this acetylation decreases SOD2 activity. Mitochondrial deacetylase SIRT3 binds to, deacetylates and activates SOD2. Increase of reactive oxygen species (ROS) levels stimulates SIRT3 transcription, leading to SOD2 deacetylation and activation. SOD2-mediated ROS reduction is synergistically increased by SIRT3 co-expression, but is cancelled by SIRT3 depletion. These results reveal a new post-translational regulation of SOD2 by means of acetylation and SIRT3-dependent deacetylation in response to oxidative stress

Acetylation Regulates Gluconeogenesis by Promoting PEPCK1 Degradation via Recruiting the UBR5 Ubiquitin Ligase

Protein acetylation has emerged as a major mechanism in regulating cellular metabolism. Whereas most glycolytic steps are reversible, the reaction catalyzed by pyruvate kinase is irreversible and the reverse reaction requires phosphoenolpyruvate carboxykinase (PEPCK1) to commit for gluconeogenesis. Here we show that acetylation regulates the stability of the gluconeogenic rate limiting enzyme PEPCK1, thereby modulating cellular response to glucose. High glucose destabilizes PEPCK1 by stimulating its acetylation. PEPCK1 is acetylated by the P300 acetyltransferase and this acetylation stimulates the interaction between PEPCK1 and UBR5, a HECT domain containing E3 ubiquitin ligase, therefore promoting PEPCK1 ubiquitinylation and degradation. Conversely, SIRT2 deacetylates and stabilizes PEPCK1. These observations represent an example that acetylation targets a metabolic enzyme to a specific E3 ligase in response to metabolic condition changes. Given that increased levels of PEPCK is linked with type II diabetes, this study also identifies potential therapeutic targets for diabetes

Theorems of complete convergence and complete integral convergence for END random variables under sub-linear expectations

Abstract The goal of this paper is to build complete convergence and complete integral convergence for END sequences of random variables under sub-linear expectation space. By using the Markov inequality, we extend some complete convergence and complete integral convergence theorems for END sequences of random variables when we have a sub-linear expectation space, and we provide a way to learn this subject

The Hippo–YAP pathway in organ size control and tumorigenesis: an updated version

The Hippo signaling pathway is gaining recognition as an important player in both organ size control and tumorigenesis, which are physiological and pathological processes that share common cellular signaling mechanisms. Upon activation by stimuli such as high cell density in cell culture, the Hippo pathway kinase cascade phosphorylates and inhibits the Yes-associated protein (YAP)/TAZ transcription coactivators representing the major signaling output of the pathway. Altered gene expression resulting from YAP/TAZ inhibition affects cell number by repressing cell proliferation and promoting apoptosis, thereby limiting organ size. Recent studies have provided new insights into the Hippo signaling pathway, elucidating novel phosphorylation-dependent and independent mechanisms of YAP/Yki inhibition by the Hippo pathway, new Hippo pathway components, novel YAP target transcription factors and target genes, and the three-dimensional structure of the YAP–TEAD complex, and providing further evidence for the involvement of YAP and the Hippo pathway in tumorigenesis

Brain Radiotherapy Combined with Sequential Chemotherapy in Non-Small-Cell Lung Cancer Patients with Brain Metastases

Background and objective Brain irradiation is the traditional treatment for NSCLC patients with brain metastases, whereas combined with chemotherapy is the nowadays treatment direction. Since sequential/maintenance chemotherapy has shown promising results in advanced NSCLC, we carried out the study to explore the role of sequential chemotherapy combined with brain radiotherapy in patients with brain metastases. Methods Treatment naïve NSCLC patients with brain metastases sequentially received the 3 chemotherapy regimens TP-NP-GP. The TP regimen consisted of Paclitaxol 175 mg/m2 d1, Cisplatin 20 mg/m2 d1-5. The NP regimen consisted of Nevalbine 25 mg/m2 d1 and 8, Cisplatin 20 mg/m2 d1-5. The GP regimen consisted of Gemcitabine 1 g/m2 d1 and 8, Cisplatin 20 mg/m2 d1-5. All regimens were repeated every 3 weeks. Each regimen was executed for at least 2 cycles and no more than 4 cycles. Results The response rates of TP, NP and GP sequentially used were 41.2%, 35.6% and 27.8% respectively for the out brain lesions and 60.8% for the brain lesions combining with brain irradiation. Median survival time was 14.7 months and the 1, 2 and 3 year overall survivals were 67.8%, 20.6% and 1.3% respectively. Conclusion The 3rd generation regimen-based sequential chemotherapy combined with WBRT was effective for NSCLC patients with brain metastasis with an encouraging survival and acceptable tolerability