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Non-canonical Notch Signaling Regulates Actin Remodeling in Cell Migration by Activating PI3K/AKT/Cdc42 Pathway
In conclusion, our research results indicate that DAPT activates PI3K/AKT/Cdc42 signaling by non-canonical Notch pathway, and the activated Cdc42 promotes the filopodia formation and inhibits lamellipodia assembly, resulting in reduced migration of breast cancer cells. The results imply that non-canonical Notch signaling may play a very important role in the rapid response of cells to the extracellular signals. Author Contributions LG, JD, and LL designed the study and wrote and revised the manuscript. LL and LZ performed most of the experiments and data analysis. SZ, X-YZ, P-XM, Y-DM, Y-YW, YC, S-JT, and Y-JZ assisted i...
Source: Frontiers in Pharmacology - April 15, 2019 Category: Drugs & Pharmacology Source Type: research

Autophagy Is a Defense Mechanism Inhibiting Invasion and Inflammation During High-Virulent Haemophilus parasuis Infection in PK-15 Cells
In this study, we sought to investigate whether SH0165 (serovar 5, high-virulent strain) and HN0001 (serovar 6, non-virulent strain) infection induces autophagy and the specific role of autophagy in bacterial invasion and inflammation during H. parasuis infection. Moreover, we explored the mechanism underlying autophagy regulated inflammation through inflammatory signaling cascades during H. parasuis infection. This observation could provide useful information for further understanding the role of autophagy in H. parasuis infection and improve our knowledge of new strategies against this pathogen. Materials and Methods B...
Source: Frontiers in cellular and infection microbiology - April 15, 2019 Category: Microbiology Source Type: research

Why Do Birds Flock? A Role for Opioids in the Reinforcement of Gregarious Social Interactions
Conclusion We propose that studies of songbirds reveal a novel network model for the integration of positive and negative reinforcement processes in non-sexual affiliative social behavior. Most studies on affiliative behavior focus on the positive affective state induced by social contact that rewards individuals interacting together. However, this review highlights that in social animals, affiliative contact is also reinforced because it reduces a negative affective state caused by social exclusion or isolation, thus creating a complementary system (i.e., positive reinforcement from affiliative interactions and negative ...
Source: Frontiers in Physiology - April 11, 2019 Category: Physiology Source Type: research

SOCS and Herpesviruses, With Emphasis on Cytomegalovirus Retinitis
Christine I. Alston1,2 and Richard D. Dix1,2* 1Department of Biology, Viral Immunology Center, Georgia State University, Atlanta, GA, United States 2Department of Ophthalmology, Emory University School of Medicine, Atlanta, GA, United States Suppressor of cytokine signaling (SOCS) proteins provide selective negative feedback to prevent pathogeneses caused by overstimulation of the immune system. Of the eight known SOCS proteins, SOCS1 and SOCS3 are the best studied, and systemic deletion of either gene causes early lethality in mice. Many viruses, including herpesviruses such as herpes simplex virus and cytomega...
Source: Frontiers in Immunology - April 10, 2019 Category: Allergy & Immunology Source Type: research

Hepatoma-Derived Growth Factor and DDX5 Promote Carcinogenesis and Progression of Endometrial Cancer by Activating β-Catenin
Conclusion: Our results provide novel evidence that HDGF interacts with DDX5 and promotes the progression of EC through the induction of β-catenin. Introduction Endometrial cancer (EC) comprises the most common malignancy involving the female genital tract and the fourth most common malignancy in women after breast, lung, and colorectal cancers (1). In 2012, approximately 320,000 new cases of EC were diagnosed worldwide and the incidence is increasing (2). Currently, endometrial carcinogenesis is thought to be a multi-step process involving the coordinated interaction of hormonal regulation, gene mutation, ad...
Source: Frontiers in Oncology - April 10, 2019 Category: Cancer & Oncology Source Type: research

Complement C5b-9 and Cancer: Mechanisms of Cell Damage, Cancer Counteractions, and Approaches for Intervention
In conclusion, osmotic burst of inflated complement-damaged cells may occur, but these bursts are most likely a consequence of metabolic collapse of the cell rather than the cause of cell death. The Complement Cell Death Mediator: A Concerted Action of Toxic Moieties Membrane pores caused by complement were first visualized by electron microscopy on red blood cell membranes as large ring structures (22). Similar lesions were viewed on E. coli cell walls (23). Over the years, ample information on the fine ultrastructure of the MAC that can activate cell death has been gathered (24) and has been recently further examined (...
Source: Frontiers in Immunology - April 9, 2019 Category: Allergy & Immunology Source Type: research

The Functions of Non-coding RNAs in rRNA Regulation
Qi Yan1, Chengming Zhu1, Shouhong Guang1,2* and Xuezhu Feng1* 1Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, China 2CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Hefei, China Ribosomes are ribonucleoprotein machines that decode the genetic information embedded in mRNAs into polypeptides. Ribosome biogenesis is tightly coordinated and controlled from the transcription of pre-rRNAs to the assembly of ribosomes. Defects or disorders in rRNA production result in a number of human ri...
Source: Frontiers in Genetics - April 4, 2019 Category: Genetics & Stem Cells Source Type: research

PAK kinase inhibition has therapeutic activity in novel preclinical models of Adult T-cell Leukemia/Lymphoma.
CONCLUSIONS: PAK2, a gene frequently amplified in ATLL, facilitates CADM1-mediated stromal interaction and promotes survival of ATLL cells. Taken together, PAK inhibition may hold significant promise as a targeted therapy for aggressive ATLLs. PMID: 30862694 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - March 11, 2019 Category: Cancer & Oncology Authors: Chung EYL, Mai Y, Shah UA, Wei Y, Ishida E, Kataoka K, Ren X, Pradhan K, Bartholdy B, Wei X, Zou Y, Zhang J, Ogawa S, Steidl U, Zang X, Verma A, Janakiram M, Ye BH Tags: Clin Cancer Res Source Type: research

Epigenetic Targeting DNMT1 of Pancreatic Ductal Adenocarcinoma using interstitial control release biodegrading polymer reduced tumor growth through Hedgehog pathway inhibition
Publication date: Available online 29 October 2018Source: Pharmacological ResearchAuthor(s): Mao-Hsuan Huang, Yi-Wen Chou, Ming-Hsun Li, Tina E. Shih, Shinn-Zong Lin, Hong-Meng Chuang, Tzyy-Wen Chiou, Hong-Lin Su, Horng-Jyh HarnAbstractAnnually, 48,000 people die from pancreatic ductal adenocarcinoma (PDAC), ranking it the fourth among cancer-related deaths in the United States. Currently, anti-cancer drugs are not effective against PDAC, and only extends survival by 3 months. Aberrant DNA methylation has been shown to play an important role during carcinogenesis in PDAC, with approximately 80% of tumor overexpressing the ...
Source: Pharmacological Research - October 30, 2018 Category: Drugs & Pharmacology Source Type: research

Staphylococcus aureus alpha toxin activates Notch in vascular cells
AbstractStaphylococcus aureus infection is one of the leading causes of morbidity in hospitalized patients in the United States, an effect compounded by increasing antibiotic resistance. The secreted agent hemolysin alpha toxin (Hla) requires the receptor A Disintegrin And Metalloproteinase domain-containing protein 10 (ADAM10) to mediate its toxic effects. We hypothesized that these effects are in part regulated by Notch signaling, for which ADAM10 activation is essential. Notch proteins function in developmental and pathological angiogenesis via the modulation of key pathways in endothelial and perivascular cells. Thus, ...
Source: Angiogenesis - October 15, 2018 Category: Molecular Biology Source Type: research

Bioreducible Poly(Amino Ethers) Based mTOR siRNA Delivery for Lung Cancer
ConclusionsThe results demonstrate that the mPAE polymer based NPs show strong potential for siRNA delivery to lung cancer cells. It is anticipated that future modification can help improve the efficacy of nucleic acid delivery, leading to higher inhibition of lung cancer growthin vitro andin vivo.
Source: Pharmaceutical Research - August 13, 2018 Category: Drugs & Pharmacology Source Type: research

Comparison of epithelial mesenchymal transition mediated tyrosine kinase inhibitor resistance in non-small cell lung cancer cell lines with wild type EGFR and mutant type EGFR.
This study investigates the role of epithelial-mesenchymal transition (EMT) in the development of resistance against TKIs in NSCLC. Currently, the role of p120-catenin, Kaiso factor and PRMT-1 in reversal of EMT in T790M mutated and TKI-resistant NSCLC cells is a new line of study. In this investigation we found upregulation of cytoplasmic p120-catenin, and it was co-localized with Kaiso factor. In the nucleus, binding of p120-catenin to Kaiso factor initiates transcription by activating EMT-transcription factors such as Snail, Slug, Twist, and ZEB1. PRMT-1 was also found to be upregulated, which induces methylation of Twi...
Source: Biochemical and Biophysical Research communications - January 11, 2018 Category: Biochemistry Authors: Iderzorig T, Kellen J, Osude C, Singh S, Woodman JA, Garcia C, Puri N Tags: Biochem Biophys Res Commun Source Type: research

Shared genetic regulatory networks for cardiovascular disease and type 2 diabetes in multiple populations of diverse ethnicities in the United States
by Le Shu, Kei Hang K. Chan, Guanglin Zhang, Tianxiao Huan, Zeyneb Kurt, Yuqi Zhao, Veronica Codoni, David-Alexandre Tr égouët, Cardiogenics Consortium , Jun Yang, James G. Wilson, Xi Luo, Daniel Levy, Aldons J. Lusis, Simin Liu, Xia Yang Cardiovascular diseases (CVD) and type 2 diabetes (T2D) are closely interrelated complex diseases likely sharing overlapping pathogenesis driven by aberrant activities in gene networks. However, the molecular circuitries underlying the pathogenic commonalities remain poorly understood. We sought t o identify the shared gene networks and their key intervening drivers for both CVD and T2...
Source: PLoS Genetics - September 28, 2017 Category: Genetics & Stem Cells Authors: Le Shu Source Type: research

Regulation of Chromatin Assembly and Cell Transformation by Formaldehyde Exposure in Human Cells
Conclusions: We propose that the inhibition of chromatin assembly represents a novel mechanism of cell transformation induced by the environmental and occupational chemical carcinogen FA. https://doi.org/10.1289/EHP1275 Received: 25 October 2016 Revised: 19 May 2017 Accepted: 23 May 2017 Published: 21 September 2017 Address correspondence to C. Jin, Dept. of Environmental Medicine, New York University School of Medicine, 57 Old Forge Rd., Tuxedo Park, NY 10987 USA. Telephone: (845) 731-3602. Email: Chunyuan.jin@nyumc.org *Current affiliation: Medical School of Nanjing University, Nanjing, China. †Current affiliatio...
Source: EHP Research - September 21, 2017 Category: Environmental Health Authors: Daniil Lyalko Tags: Research Source Type: research

Exportin 1 (XPO1) inhibition leads to restoration of tumor suppressor miR-145 and consequent suppression of pancreatic cancer cell proliferation and migration.
In this study, we found that the expression of miR-145 was significantly lower in PDAC cells when compared to normal pancreatic duct epithelial cells. Here we show that inhibition of the nuclear exporter protein exportin 1 (XPO1; also known as chromosome maintenance region 1 [CRM1]) by siRNA knockdown or by the Selective Inhibitor of Nuclear Export (SINE) compound (KPT-330; selinexor) increases miR-145 expression in PDAC cells resulting in the decreased cell proliferation and migration capacities. A similar result was obtained with forced expression of miR-145 in PDAC cells. To this end, SINE compound treatment mediated th...
Source: Oncotarget - July 29, 2017 Category: Cancer & Oncology Tags: Oncotarget Source Type: research