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https://www.readbyqxmd.com/read/28214331/pomc-maintains-tumor-initiating-properties-of-tumor-tissue-derived-long-term-cultured-breast-cancer-stem-cells
#1
Xiaoti Lin, Weiyu Chen, Fengqin Wei, Binhua P Zhou, Mien-Chie Hung, Xiaoming Xie
The identification and understanding of the molecular network of cancer stem cells (CSCs) have had a profound impact on our view of carcinogenesis and treatment strategy. Unfortunately, a major problem is that serial passages of CSCs from clinical solid tumor specimens currently are not available in any lab, and thus, reported data are difficult to confirm and intensively interrogated. Here, we have generated two tumor tissue-derived breast CSC (BCSC) lines that showed prolonged maintenance over 20 serial passages in vitro, while retaining their tumor-initiating biological properties...
February 18, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28214294/ptk6-localized-at-the-plasma-membrane-promotes-cell-proliferation-and-migration-through-phosphorylation-of-eps8
#2
Won-Sik Shin, Hyun Jae Shim, Young Hun Lee, Minju Pyo, Jun Sang Park, So Yun Ahn, Seung-Taek Lee
Protein tyrosine kinase 6 (PTK6; also known as Brk) is closely related to the Src family kinases, but lacks a membrane-targeting myristoylation signal. Sublocalization of PTK6 at the plasma membrane enhances its oncogenic potential. To understand the mechanism(s) underlying the oncogenic property of plasma-membrane-associated PTK6, proteins phosphorylated by membrane-targeted myristoylated PTK6 (Myr-PTK6) were enriched and analyzed using a proteomics approach. Eps8 which was identified by this method is phosphorylated by Myr-PTK6 in HEK293 cells...
February 18, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28214253/long-noncoding-rna-linc00673-is-activated-by-sp1-and-exerts-oncogenic-properties-by-interacting-with-lsd1-and-ezh2-in-gastric-cancer
#3
Mingde Huang, Jiakai Hou, Yunfei Wang, Min Xie, Chenchen Wei, Fengqi Nie, Zhaoxia Wang, Ming Sun
Long noncoding RNAs (lncRNAs) have emerged as important regulators in a variety of human diseases, including cancers. However, the biological function of these molecules and the mechanisms responsible for their alteration in gastric cancer (GC) are not fully understood. In this study, we found that lncRNA LINC00673 is significantly upregulated in gastric cancer. Knockdown of LINC00673 inhibited cell proliferation and invasion and induced cell apoptosis, whereas LINC00673 overexpression had the opposite effect...
February 14, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28214206/involvement-of-prolyl-isomerase-pin1-in-the-cell-cycle-progression-and-proliferation-of-hepatic-oval-cells
#4
Prabodh Risal, Nirajan Shrestha, Lokendra Chand, Karl G Sylvester, Yeon Jun Jeong
Liver regenerates remarkably after toxic injury or surgical resection. In the case of failure of resident hepatocytes to restore loss, repopulation is carried out by induction, proliferation, and differentiation of the progenitor cell. Although, some signaling pathways have been verified to contribute oval cell-mediated liver regeneration, role of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1(Pin1) in the oval cells proliferation is unknown. In the present study, we evaluate the role of Pin1 in oval cells proliferation...
January 18, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28213977/mitochondria-targeted-esculetin-inhibits-pai-1-levels-by-modulating-stat3-activation-and-mir-19b-via-sirt3-role-in-acute-coronary-artery-syndrome
#5
Sujana Katta, Santosh Karnewar, Devayani Panuganti, Mahesh Kumar Jerald, Sastry B K, Srigiridhar Kotamraju
In this study, we explored the microRNAs responsible for the regulation of PAI-1 during LPS-stimulated inflammation in human aortic endothelial cells, subsequently studied the effect of a newly synthesized mitochondria-targeted esculetin (Mito-Esc) that was shown for its anti-atherosclerotic potential in modulating PAI-1 levels and its targeted miRs during angiotensin-II-induced atherosclerosis in ApoE(-/-) mice. LPS-stimulated PAI-1 was accompanied with an upregulation of miR-19b and down-regulation of miR-30c...
February 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28213973/transforming-growth-factor-%C3%AE-induces-bone-marrow-mesenchymal-stem-cell-migration-via-noncanonical-signals-and-n-cadherin
#6
Maria Jose Dubon, Jinyeong Yu, Sanghyuk Choi, Ki-Sook Park
Transforming growth factor-beta (TGF-β) induces the migration and mobilization of bone marrow-derived mesenchymal stem cells (BM-MSCs) to maintain bone homeostasis during bone remodeling and facilitate the repair of peripheral tissues. Although many studies have reported the mechanisms through which TGF-β mediates the migration of various types of cells, including cancer cells, the intrinsic cellular mechanisms underlying cellular migration and mobilization of BM-MSCs mediated by TGF-β are unclear. In this study, we showed that TGF-β activated noncanonical signaling molecules, such as Akt, extracellular signal-regulated kinase 1/2 (ERK1/2), focal adhesion kinase (FAK), and p38, via TGF-β type I receptor in human BM-MSCs and murine BM-MSC-like ST2 cells...
February 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28213967/extracellular-vesicles-from-bone-marrow-derived-mesenchymal-stem-cells-improve-survival-from-lethal-hepatic-failure-in-mice
#7
Hiroaki Haga, Irene K Yan, Kenji Takahashi, Akiko Matsuda, Tushar Patel
Stem cell-based therapies have potential for treatment of liver injury by contributing to regenerative responses, through functional tissue replacement or paracrine effects. The release of extracellular vesicles (EV) from cells has been implicated in intercellular communication, and may contribute to beneficial paracrine effects of stem cell-based therapies. Therapeutic effects of bone-marrow derived mesenchymal stem cells (MSC) and vesicles released by these cells were examined in a lethal murine model of hepatic failure induced by d-galactosamine/tumor necrosis factor-α (TNF-α)...
February 18, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28213613/an-atf4-atg5-signaling-in-hypothalamic-pomc-neurons-regulates-fat-mass-via-affecting-energy-expenditure
#8
Yuzhong Xiao, Yalan Deng, Feixiang Yuan, Tingting Xia, Hao Liu, Zhigang Li, Zhixue Liu, Hao Ying, Yi Liu, Qiwei Zhai, Shanghai Chen, Feifan Guo
Although many biological functions of activating transcription factor 4 (ATF4) have been identified, a role of hypothalamic ATF4 in the regulation of energy homeostasis is poorly understood. Here, we showed that hypothalamic pro-opiomelanocortin (POMC) neurons specific ATF4 knockout (PAKO) mice are lean and have higher energy expenditure. Furthermore, PAKO mice were resistant to high-fat diet (HFD)-induced obesity, glucose intolerance and leptin resistance. Moreover, the expression of autophagy protein 5 (ATG5) was increased or decreased by ATF4 knockdown or over-expression, respectively, and ATF4 inhibited the transcription of ATG5 by binding to the basic zipper-containing protein (bZIP) sites on its promoter...
February 17, 2017: Diabetes
https://www.readbyqxmd.com/read/28213560/identification-of-putative-substrates-of-sec2-a-chloroplast-inner-envelope-translocase
#9
Yubing Li, Jonathan R Martin, Giovanni A Aldama, Donna E Fernandez, Kenneth Cline
Most chloroplast proteins are synthesized in the cytosol and imported into chloroplasts. Many imported proteins are further targeted to the thylakoid membrane and lumen by the SEC1, TAT or SRP/ALB3 translocases. Others are targeted to the inner chloroplast envelope membrane by un-described translocase(s). Recently, a second SEC system (SEC2) consisting of SCY2, SECE2, and SECA2 was found in the chloroplast envelope. Null mutants of SCY2 in Arabidopsis exhibit a severe embryo lethal phenotype. To investigate the function of SEC2 system in plants, we used inducible RNAi to knockdown SCY2 in Arabidopsis...
February 17, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28213467/hypoxia-induces-arginase-ii-expression-and-increases-viable-human-pulmonary-artery-smooth-muscle-cell-numbers-via-ampk%C3%AE-1-signaling
#10
Jianjing Xue, Leif D Nelin, Bernadette Chen
Pulmonary artery smooth muscle cell (PASMC) proliferation is one of the hallmark features of hypoxia-induced pulmonary hypertension. With only supportive treatment options available for this life threatening disease, treating and preventing the proliferation of PASMCs is a viable therapeutic option. A key promoter of hypoxia-induced increases in the number of viable human PASMCs is arginase II, with attenuation of viable cell numbers following pharmacologic inhibition or siRNA knockdown of the enzyme. Additionally, increased levels of arginase have been demonstrated in the pulmonary vasculature of patients with pulmonary hypertension...
February 17, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28213356/otx2-activity-at-distal-regulatory-elements-shapes-the-chromatin-landscape-of-group-3-medulloblastoma
#11
Gaylor Boulay, Mary E Awad, Nicolo Riggi, Tenley C Archer, Sowmya Iyer, Wannaporn E Boonseng, Nikki E Rossetti, Beverly Naigles, Shruthi Rengarajan, Angela Volorio, James C Kim, Jill P Mesirov, Pablo Tamayo, Scott L Pomeroy, Martin J Aryee, Miguel N Rivera
Medulloblastoma is the most frequent malignant pediatric brain tumor and is divided into at least four subgroups known as WNT, SHH, Group 3, and Group 4. Here, we characterized gene regulation mechanisms in the most aggressive subtype, Group 3 tumors, through genome-wide chromatin and expression profiling. Our results show that most active distal sites in these tumors are occupied by the transcription factor OTX2. Highly active OTX2-bound enhancers are often arranged as clusters of adjacent peaks and are also bound by the transcription factor NEUROD1...
February 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28213203/ghrelin-s-control-of-food-reward-and-body-weight-in-the-lateral-hypothalamic-area-is-sexually-dimorphic
#12
Lorena López-Ferreras, Jennifer E Richard, Rozita H Anderberg, Fredrik H Nilsson, Kajsa Olandersson, Scott E Kanoski, Karolina P Skibicka
Ghrelin is a stomach-produced hormone that stimulates ingestive behavior and increases motivated behavior to obtain palatable foods. Ghrelin receptors (growth hormone secretagogue receptors; Ghsr) are expressed in the lateral hypothalamic area (LHA), and LHA-targeted ghrelin application increases ingestive behavior in male rodents. However, the effects of LHA ghrelin signaling in females are unexplored. Here we investigated whether LHA ghrelin signaling is necessary and sufficient for control of ingestive and motivated behavior for food in male and female rats...
February 14, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28213130/dipeptidyl-peptidase-4-impairs-insulin-signalling-and-promotes-lipid-accumulation-in-hepatocytes
#13
Kerstin Rufinatscha, Bernhard Radlinger, Jochen Dobner, Sabrina Folie, Claudia Bon, Elisabeth Profanter, Claudia Ress, Karin Salzmann, Gabriele Staudacher, Herbert Tilg, Susanne Kaser
Dipeptidyl-peptidase 4 [DPP-4) has evolved into an important target in diabetes therapy due to its role in incretin hormone metabolism. In contrast to its systemic effects, cellular functions of membranous DPP-4 are less clear. Here we studied the role of DPP-4 in hepatic energy metabolism. In order to distinguish systemic from cellular effects we established a cell culture model of DPP-4 knockdown in human hepatoma cell line HepG2. DPP-4 suppression was associated with increased basal glycogen content due to enhanced insulin signalling as shown by increased phosphorylation of insulin-receptor substrate 1 (IRS-1), protein kinase B/Akt and mitogen-activated protein kinases (MAPK)/ERK, respectively...
February 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28212834/death-associated-protein-1-dap-1-positively-regulates-virus-replication-and-apoptosis-of-hemocytes-in-shrimp-marsupenaeus-japonicus
#14
Wen-Li Xia, Li-Hua Kang, Chang-Bin Liu, Cui-Jie Kang
Death-associated protein 1 (DAP1) is a small proline-rich cytoplasmic protein that functions both in the apoptosis and autophage process of mammalian and in the clinical cancer of human. However, little knowledge is known about the homologue gene of DAP1 and its roles in the physiological process of invertebrates. In this paper, we report a novel function of DAP1 in the antivirus immunity of shrimp. A homologue gene of DAP1 was cloned from Marsupenaeus japonicus and named as Mjdap-1. The full-length of Mjdap-1 was 1761 bp with a 309 bp open reading frame that encoded 102 amino acids...
February 14, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28212576/galectin-1-knockdown-improves-drug-sensitivity-of-breast-cancer-by-reducing-p-glycoprotein-expression-through-inhibiting-the-raf-1-ap-1-signaling-pathway
#15
Fang Wang, Pengwei Lv, Yuanting Gu, Lin Li, Xin Ge, Guangcheng Guo
Galectin-1 (Gal-1), a member of the galectin family of carbohydrate binding proteins, plays a pivotal role in various cellular processes of tumorigenesis. The regulatory effect of Gal-1 on multidrug resistance (MDR) breast cancer cells is still unclear. qRT-PCR and western blot showed that Gal-1 and MDR gene 1 (MDR1) were both highly expressed in breast tumor tissues and cell lines. MTT assay and flow cytometry revealed that Gal-1 knockdown improved sensitivity to paclitaxel (PTX) and adriamycin (ADR) in MCF-7/PTX and MCF-7/ADR cells via inhibition of cell viability and promotion of cell apoptosis, while MDR1 overexpression weakened the sensitivity to PTX and ADR induced by Gal-1 knockdown...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212573/dynamic-variations-in-epithelial-to-mesenchymal-transition-emt-atm-and-slfn11-govern-response-to-parp-inhibitors-and-cisplatin-in-small-cell-lung-cancer
#16
C Allison Stewart, Pan Tong, Robert J Cardnell, Triparna Sen, Lerong Li, Carl M Gay, Fatemah Masrorpour, You Fan, Rasha O Bara, Ying Feng, Yuanbin Ru, Junya Fujimoto, Samrat T Kundu, Leonard E Post, Karen Yu, Yuqiao Shen, Bonnie S Glisson, Ignatio Wistuba, John V Heymach, Don L Gibbons, Jing Wang, Lauren Averett Byers
Small cell lung cancer (SCLC) is one of the most aggressive forms of cancer, with a 5-year survival <7%. A major barrier to progress is the absence of predictive biomarkers for chemotherapy and novel targeted agents such as PARP inhibitors. Using a high-throughput, integrated proteomic, transcriptomic, and genomic analysis of SCLC patient-derived xenografts (PDXs) and profiled cell lines, we identified biomarkers of drug sensitivity and determined their prevalence in patient tumors. In contrast to breast and ovarian cancer, PARP inhibitor response was not associated with mutations in homologous recombination (HR) genes (e...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212558/ataxin-1-regulates-epithelial-mesenchymal-transition-of-cervical-cancer-cells
#17
A-Ram Kang, Hyoung-Tae An, Jesang Ko, Seongman Kang
The mutant form of the protein ataxin-1 (ATXN1) causes the neurodegenerative disease spinocerebellar ataxia type-1. Recently, ATXN1 was reported to enhance E-cadherin expression in the breast cancer cell line MCF-7, suggesting a potential association between ATXN1 and cancer development. In the present study, we discovered a novel mechanism through which ATXN1 regulates the epithelial-mesenchymal transition (EMT) of cancer cells. Hypoxia-induced upregulation of the Notch intracellular domain expression decreased ATXN1 expression via MDM2-associated ubiquitination and degradation...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212444/sumo-modification-of-a-heterochromatin-histone-demethylase-jmjd2a-enables-viral-gene-transactivation-and-viral-replication
#18
Wan-Shan Yang, Mel Campbell, Pei-Ching Chang
Small ubiquitin-like modifier (SUMO) modification of chromatin has profound effects on transcription regulation. By using Kaposi's sarcoma associated herpesvirus (KSHV) as a model, we recently demonstrated that epigenetic modification of viral chromatin by SUMO-2/3 is involved in regulating gene expression and viral reactivation. However, how this modification orchestrates transcription reprogramming through targeting histone modifying enzymes remains largely unknown. Here we show that JMJD2A, the first identified Jumonji C domain-containing histone demethylase, is the histone demethylase responsible for SUMO-2/3 enrichment on the KSHV genome during viral reactivation...
February 17, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28211985/a-girl-with-developmental-delay-ataxia-cranial-nerve-palsies-severe-respiratory-problems-in-infancy-expanding-ndst1-syndrome
#19
Linlea Armstrong, Maja Tarailo-Graovac, Graham Sinclair, Kimberly I Seath, Wyeth W Wasserman, Colin J Ross, Clara D M van Karnebeek
NDST1 encodes an enzyme involved in the first steps in the synthesis of heparan sulfate chains, proteoglycans that are regulators found on the cell surface and in the extracellular matrix. Eight individuals homozygous for one of four family-specific missense mutations in the sulfotransferase domain of the enzyme have been described. They have intellectual disability. Some additionally had hypotonia, ataxia. seizures, and/or short stature, but none had history of respiratory problems. No humans with homozygous null mutations are known...
March 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28211965/first-synthesis-of-an-oridonin-conjugated-iridium-iii-complex-for-the-intracellular-tracking-of-nf-%C3%AE%C2%BAb-in-living-cells
#20
Wanhe Wang, Chao Yang, Sheng Lin, Kasipandi Vellaisamy, Guodong Li, Weihong Tan, Chung-Hang Leung, Dik-Lung Ma
NF-κB is a critical transcription factor that plays an important role in mediating inflammation, the immune response, and cell proliferation. The activation of NF-κB leads to an enhancement of proinflammatory mediator expression, which is implicated in the pathogenesis of a variety of diseases. Therefore, methods that allow the intracellular tracking of NF-κB are particularly attractive as they can provide information regarding the pathways or stimulation responses that are involved in the activation of NF-κB...
February 17, 2017: Chemistry: a European Journal
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