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Integrin apoptosis

Zhenhui Wang, Chenghua Li, Ronglian Xing, Yina Shao, Xuelin Zhao, Weiwei Zhang, Ming Guo
Lipopolysaccharides (LPS) can induce the apoptosis of coelomocytes in Apostichopus japonicus (A. japonicus), and β-integrin serves as an apoptotic inhibitor during this process. However, the underlying mechanism in invertebrates is largely unknown. Integrin/focal adhesion kinase (FAK) signaling pathway modulates the apoptosis in vertebrates. In this study, a novel FAK was identified from A. japonicus (designated as AjFAK) by β-integrin (designated as AjITGB) -mediated GST-pull down assay. This interaction was further validated in the LPS-exposed coelomocytes through co-immunoprecipitation and immunofluorescence analyses...
October 16, 2018: Developmental and Comparative Immunology
Jiao Xu, Tuochen Zheng, Wenli Hong, Haifeng Ye, Chuan Hu, Yuehui Zheng
The ovary is surrounded by a whitish layer of mesodermally derived ovarian surface epithelium (OSE) that lines the intraembryonic celom and comprises simple squamous to cuboidal to low pseudostratified columnar epithelial cells. Its integrity is maintained by simple desmosomes, incomplete tight junctions, several integrins and cadherins. Recent research has found that ovarian stem cells (OSCs) exist within the OSE and may be responsible for both neo-oogenesis and ovarian cancer during adult life. The factors determining whether OSCs undergo neo-oogenesis or ovarian cancer are of great interest to researchers and clinicians...
October 18, 2018: Cellular Physiology and Biochemistry
Geng Chen, Lv Xiong, Yumeng Wang, Libo He, Rong Huang, Lanjie Liao, Zuoyan Zhu, Yaping Wang
Integrin β-1 (ITGB1) is a transmembrane protein belonging to the integrin family and it plays an important role in viral entry. In this study, the itgb1b gene of the rare minnow, Gobiocypris rarus , was cloned and analyzed. To investigate the possible role of itgb1b on grass carp reovirus (GCRV) infection, we generated an ITGB1b-deficient rare minnow (ITGB1b-/- ) using the CRISPR/Cas9 system. Following stimulation with GCRV, the survival time of the -ITGB1b-/- rare minnows was extended in comparison to the wild-type minnows...
October 15, 2018: International Journal of Molecular Sciences
Yanping Lu, Shunping Han, Hongyue Zheng, Rui Ma, Yuting Ping, Jiafeng Zou, Hongxia Tang, Yongping Zhang, Xiuling Xu, Fanzhu Li
Background: The Traditional Chinese Medicine, arsenic trioxide (ATO, As2 O3 ) could inhibit growth and induce apoptosis in a variety of solid tumor cells, but it is severely limited in the treatment of glioma due to its poor BBB penetration and nonspecifcity distribution in vivo. Purpose: The objective of this study was encapsulating ATO in the modified PAMAM den-drimers to solve the problem that the poor antitumor effect of ATO to glioma, which provide a novel angle for the study of glioma treatment...
2018: International Journal of Nanomedicine
Ioannis Gkouveris, Nikolaos G Nikitakis, Jaya Asservatham, Kalu U E Ogbureke
The expression of proinflammatory cytokines in various malignant neoplasms is widely considered to represent the host immune response to tumor development. The role of interferon (IFN)γ in head and neck squamous cell carcinoma, and its association with endoplasmic reticulum (ER) stress pathways, remains a subject of ongoing investigation. Dentin sialophosphoprotein (DSPP), which is a member of the small integrin‑binding N‑linked glycoproteins family, has been implicated in malignant transformation and invasion of oral squamous cell carcinoma (OSCC)...
October 10, 2018: International Journal of Oncology
Bohong Cen, Yuanyi Wei, Wen Huang, Muzhou Teng, Shuai He, Jianlong Li, Wei Wang, Guolin He, Xin Bai, Xiaoxia Liu, Yawei Yuan, Xinghua Pan, Aimin Ji
The PI3K-AKT-mTOR-signaling pathway is frequently activated in glioblastoma (GBM). Inhibition of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta (PIK3CB)/p110β (a PI3K catalytic isoform) by RNAi substantially suppresses GBM growth with less toxicity to normal astrocytes. However, insufficient and non-specific small interfering RNA (siRNA) delivery may limit the efficacy of RNAi-based therapies against GBM. Here we prepared a novel methoxy-modified PIK3CB siRNA molecule (siPIK3CB) that was covalently conjugated to a [cyclo(Arg-Gly-Asp-D-Phe-Lys)-Ahx]2 -Glu-PEG-MAL (biRGD) peptide, which selectively binds to integrin αvβ3 receptors...
September 6, 2018: Molecular Therapy. Nucleic Acids
Zhen Wang, Tatiana Boyko, Misha C Tran, Marie LaRussa, Namrata Bhatia, Vania Rashidi, Michael T Longaker, George P Yang
BACKGROUND: Osteoarthritis (OA) is a debilitating disease process, affecting mobility and overall health of millions. Current treatment is for symptomatic relief and discovery of approaches to halt or reverse damage is imperative. Deletion of developmental endothelial locus-1 (Del1) has been shown to increase severity of OA in knockout mice. We examined the intracellular pathways involved in the ability of DEL1 to protect chondrocytes from apoptosis and anoikis and hypothesized that it functioned via integrin signaling...
November 2018: Journal of Surgical Research
Laure Malric, Sylvie Monferran, Caroline Delmas, Florent Arnauduc, Perrine Dahan, Sabrina Boyrie, Pauline Deshors, Vincent F Lubrano, Dina Ferreira Da Mota, Julia Gilhodes, Thomas Filleron, Aurore Siegfried, Solène M Evrard, Aline Kowalski-Chauvel, Elizabeth Cohen-Jonathan Moyal, Christine Toulas, Anthony Lemarié
Glioblastomas (GBs) are malignant brain tumors with poor prognosis despite treatment with surgery and radio/chemotherapy. These tumors are defined by an important cellular heterogeneity and notably contain a subpopulation of Glioblastoma-initiating cells (GICs), which contribute to tumor aggressiveness, resistance and recurrence. Some integrins are specifically expressed by GICs and could be actionable targets to improve glioblastoma treatment. Here, integrin β8 (ITGB8) was identified as a potential selective target in this highly tumorigenic GIC subpopulation...
September 28, 2018: Molecular Cancer Research: MCR
Peter P Ruvolo
The microenvironment within the bone marrow (BM) contains support cells that promote leukemia cell survival and suppress host anti-tumor defenses. Galectins are a family of beta-galactoside binding proteins that are critical components in the tumor microenvironment. Galectin 1 (LGALS1) and Galectin 3 (LGALS3) as regulators of RAS signaling intracellularly and as inhibitors of immune cells extracellularly are perhaps the best studied members for their role in leukemia biology. Interest in Galectin 9 (LGALS9) is growing as this galectin has been identified as an immune checkpoint molecule...
September 12, 2018: Advances in Biological Regulation
Dimakatso Alice Senthebane, Tina Jonker, Arielle Rowe, Nicholas Ekow Thomford, Daniella Munro, Collet Dandara, Ambroise Wonkam, Dhirendra Govender, Bridget Calder, Nelson C Soares, Jonathan M Blackburn, M Iqbal Parker, Kevin Dzobo
BACKGROUND: The functional interplay between tumor cells and their adjacent stroma has been suggested to play crucial roles in the initiation and progression of tumors and the effectiveness of chemotherapy. The extracellular matrix (ECM), a complex network of extracellular proteins, provides both physical and chemicals cues necessary for cell proliferation, survival, and migration. Understanding how ECM composition and biomechanical properties affect cancer progression and response to chemotherapeutic drugs is vital to the development of targeted treatments...
September 20, 2018: International Journal of Molecular Sciences
Mehak Gulzar, Sunayana Begum Syed, Faez Iqbal Khan, Parvez Khan, Shahid Ali, Gulam Mustafa Hasan, Pankaj Taneja, Md Imtaiyaz Hassan
Integrin-linked kinase (ILK) is a member of Ser/Thr kinase which interacts to the cytoplasmic domain of β-integrins, and thereby induces apoptosis. ILK is considered as potential drug target because it's direct involvement in the tumor progression. Here, we have performed molecular docking followed by 100 ns MD simulation to understand the mechanism of interaction of ILK with the ellagic acid (EA). EA is well known for its antiproliferative and antioxidant properties in cancer cell lines and animal models...
September 15, 2018: International Journal of Biological Macromolecules
Xudong Li, Aiping Yin, Wenjing Zhang, Fei Zhao, Jia Lv, Jing Lv, Jiping Sun
As a common type of renal cancer, renal cell carcinoma (RCC) has a high annual mortality rate. The incidence of RCC has been increasing in China and worldwide. A large number cases of RCC are diagnosed at late stages, often with local and/or systematic metastasis. Surgical resection of RCC is only suitable for a small number of patients with early stage tumors, and thus, novel therapeutic methods are required. Junctional adhesion molecule 3 (Jam3) is a member of the junctional adhesion molecule family, which has been linked to epithelial and cancer cell proliferation...
November 2018: International Journal of Molecular Medicine
Eswara Murali Satyavarapu, Ranjita Das, Chandan Mandal, Asima Mukhopadhyay, Chitra Mandal
Cancer cells display abnormal redox metabolism. Autophagy, anoikis and reactive oxygen species (ROS) play a regulatory role during metastasis. LC3 is a well-known essential molecule for autophagy. Therefore, we wanted to explore the molecular interplay between autophagy, anoikis, and ROS in relation to LC3B. We observed enhanced LC3B level along with increased expression of p62 and modulation of other autophagy-related molecules (Atg 3, 5, 7, 12, 16L1 and Beclin1) by inducing oxidative-stress in ovarian cancer cells using a ROS-producing pro-oxidant molecule...
September 17, 2018: Cell Death & Disease
Stephanie L C Scofield, Christopher R Daniels, Suman Dalal, Jonathan A Millard, Mahipal Singh, Krishna Singh
AIMS: β-adrenergic receptor (β-AR) stimulation increases extracellular levels of ubiquitin (UB), and exogenous UB plays an important role in β-AR-stimulated myocardial remodeling with effects on heart function, fibrosis and myocyte apoptosis. Cardiac fibroblasts are vital for maintaining the normal function of the heart, and in the structural remodeling of the heart in response to injury. Here we hypothesized that extracellular UB modulates cardiac fibroblast phenotype and function via its interaction with CXC chemokine receptor type 4 (CXCR4)...
October 15, 2018: Life Sciences
Oded Komemi, Gali Epstein Shochet, Meir Pomeranz, Ami Fishman, Metsada Pasmanik-Chor, Liat Drucker, Shelly Tartakover Matalon, Michael Lishner
The extracellular matrix (ECM) affects cancer cell characteristics. Inability of normal epithelial cells to attach to the ECM induces apoptosis (anoikis). Cancer cells are often anoikis resistant, a prerequisite for their metastatic spread. Previously we demonstrated that the placenta manipulates its surrounding ECM in a way that prevents breast cancer cells (BCCL) attachment and induces their motility and aggregation. This fits with the fact that although breast cancer during pregnancy is often advanced, metastasis to the placenta is rarely observed...
September 8, 2018: International Journal of Cancer. Journal International du Cancer
Feng Tang, Lin Feng, Runle Li, Wei Wang, Huihui Liu, Quanyu Yang, Ri-Li Ge
Tang, Feng, Lin Feng, Runle Li, Wei Wang, Huihui Liu, Quanyu Yang, and Ri-Li Ge. Inhibition of suicidal erythrocyte death by chronic hypoxia. High Alt Med Biol. 00:000-000, 2018. BACKGROUND/AIMS: High-altitude polycythemia is defined by the increase of hematocrit and hemoglobin at high altitudes caused by production of excessive erythrocytes. Eryptosis is a process by which mature erythrocytes undergo self-destruction sharing several features with apoptosis. However, the eryptosis in high-altitude hypobaric hypoxia is unknown...
September 7, 2018: High Altitude Medicine & Biology
Yongliang Ni, Xin Wang, Xiaoxuan Yin, Yan Li, Xigao Liu, Haixin Wang, Xiangjv Liu, Jun Zhang, Haiqing Gao, Benkang Shi, Shaohua Zhao
Podocyte injury is an early pathological change characteristic of various glomerular diseases, and apoptosis and F-actin cytoskeletal disruption are typical features of podocyte injury. In this study, we found that adriamycin (ADR) treatment resulted in typical podocyte injury and repressed plectin expression. Restoring plectin expression protected against ADR-induced podocyte injury whereas siRNA-mediated plectin silencing produced similar effects as ADR-induced podocyte injury, suggesting that plectin plays a key role in preventing podocyte injury...
September 6, 2018: Journal of Cellular and Molecular Medicine
Hang Cao, Syed M Qadri, Elisabeth Lang, Lisann Pelzl, Anja T Umbach, Veronika Leiss, Lutz Birnbaumer, Bernd Nürnberg, Burkert Pieske, Jakob Voelkl, Meinrad Gawaz, Rosi Bissinger, Florian Lang
Gαi2 , a heterotrimeric G-protein subunit, regulates various cell functions including ion channel activity, cell differentiation, proliferation and apoptosis. Platelet-expressed Gαi2 is decisive for the extent of tissue injury following ischemia/reperfusion. However, it is not known whether Gαi2 plays a role in the regulation of platelet apoptosis, which is characterized by caspase activation, cell shrinkage and cell membrane scrambling with phosphatidylserine (PS) translocation to the platelet surface. Stimulators of platelet apoptosis include thrombin and collagen-related peptide (CoRP), which are further known to enhance degranulation and activation of αII b β3-integrin and caspases...
September 2018: Physiological Reports
Li Han, Leyuan Wang, Sha Tang, Lin Yuan, Shuangyan Wu, Xizi Du, Yang Xiang, Xiangping Qu, Huijun Liu, Huaiqing Luo, Xiaoqun Qin, Chi Liu
BACKGROUND: Chronic persistent airway inflammation has been associated with the comorbidity of asthma and bipolar disorder (BD). However, the direct relevance between airway inflammation and BD-like psychiatric comorbidity is almost unknown. Integrin β4 (ITGB4) is downregulated on the airway epithelial of asthma patients, which might play a critical role in the parthenogenesis of airway inflammation. So this study aimed to examine the role of ITGB4 deficiency in mediating airway inflammation and further leading to the BD-like behaviors...
August 31, 2018: Journal of Neuroinflammation
Florian Haun, Simon Neumann, Lukas Peintner, Katrin Wieland, Jüri Habicht, Carsten Schwan, Kristine Østevold, Maria Magdalena Koczorowska, Martin Biniossek, Matthias Kist, Hauke Busch, Melanie Boerries, Roger J Davis, Ulrich Maurer, Oliver Schilling, Klaus Aktories, Christoph Borner
Anoikis is a form of apoptosis induced by cell detachment. Integrin inactivation plays a major role in the process but the exact signalling pathway is ill-defined. Here we identify an anoikis pathway using gliotoxin (GT), a virulence factor of the fungus Aspergillus fumigatus, which causes invasive aspergillosis in humans. GT prevents integrin binding to RGD-containing extracellular matrix components by covalently modifying cysteines in the binding pocket. As a consequence, focal adhesion kinase (FAK) is inhibited resulting in dephosphorylation of p190RhoGAP, allowing activation of RhoA...
August 30, 2018: Nature Communications
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