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Toshiaki Tanaka, Kaoru Goto, Mitsuyoshi Iino
Sec8 is one of the subunits of the exocyst, which is an evolutionarily conserved complex of eight proteins, comprising Sec3 (EXOC1), Sec5 (EXOC2), Sec6 (EXOC3), Sec8 (EXOC4), Sec10 (EXOC5), Sec15 (EXOC6), Exo70 (EXOC7), and Exo84 (EXOC8) subunits. Sec8 knockout mice embryos initiate gastrulation but are unable to progress beyond the primitive streak stage and die shortly. During embryonic development, the first epithelial-mesenchymal transition (EMT) event occurs at gastrulation. Sec8 may be involved in the early embryonic development through EMT...
October 18, 2016: Cellular Signalling
J Vila, R Pariaut, N S Moïse, E M Oxford, P R Fox, C A Reynolds, C Saelinger
OBJECTIVE: To investigate the expression and distribution of desmosomal and gap junction proteins of the intercalated disc in the atria of boxers with arrhythmogenic right ventricular cardiomyopathy (ARVC). ANIMALS: Nineteen control dogs and 13 boxers with histopathologically confirmed ARVC. METHODS: Right and left atrial samples were examined using immunofluorescence and Western blots. The intercalated disc proteins investigated included total and phosphorylated connexin43 (Cx43 and pCx43), connexin45, connexin40, plakoglobin, plakophilin-2, desmoplakin, and N-cadherin...
October 18, 2016: Journal of Veterinary Cardiology: the Official Journal of the European Society of Veterinary Cardiology
Jolanda van Hengel, Celine Van den Broeke, Tim Pieters, Louis Libbrecht, Ilse Hofmann, Frans van Roy
p120 catenin (p120ctn) is required for the stability of classic cadherins at the cell surface and is thought to play a central role in modulating cell-cell adhesion. Cytoplasmic p120ctn promotes cell motility, and probably other activities, by modulating the activities of RhoA, Rac and Cdc42. E-cadherin is expressed in periportal but not in perivenous hepatocytes. In contrast, all hepatocytes of normal mouse liver express N-cadherin. Cholangiocytes express exclusively E-cadherin. Mice with p120ctn ablation in hepatocytes and cholangiocytes (p120LiKO mice) were generated by Cre-loxP technology...
October 15, 2016: European Journal of Cell Biology
Shuai Wang, Li-Jie Zhao, Yi-Chao Zheng, Dan-Dan Shen, Er-Fei Miao, Xue-Peng Qiao, Li-Juan Zhao, Ying Liu, Ruilei Huang, Bin Yu, Hong-Min Liu
A new series of [1,2,4]triazolo[1,5-a]pyrimidine-based LSD1 inhibitors were designed, synthesized, and further evaluated for their cytotoxicity against MGC-803, EC109, A549 and PC-9 cells as well as the ability of inhibiting LSD1. Some of these compounds showed potent inhibition toward LSD1 and selectively inhibited growth of A549 and PC-9 cells. Compound 6l potently inhibited growth of PC-9 cells (IC50 = 0.59 μM), about 4-fold more potent than 5-FU. Further SARs studies led to the identification of compounds 6l-m, which had good growth inhibition against all the tested cancer cell lines and were much more potent than 5-FU and GSK2879552...
October 14, 2016: European Journal of Medicinal Chemistry
Erik R Nelson, Shenduo Li, Margaret Kennedy, Sturgis Payne, Kelly Kilibarda, Jeffrey Groth, Michelle Bowie, Edgardo Parilla-Castellar, Gustaaf de Ridder, Paul Kelly Marcom, Matthew Lyes, Bercedis L Peterson, Michael Cook, Salvatore V Pizzo, Donald P McDonnell, Robin E Bachelder
BACKGROUND: Although most triple-negative breast cancer (TNBC) patients initially respond to chemotherapy, residual tumor cells frequently persist and drive recurrent tumor growth. Previous studies from our laboratory and others' indicate that TNBC is heterogeneous, being composed of chemo-sensitive and chemo-resistant tumor cell subpopulations. In the current work, we studied the invasive behaviors of chemo-resistant TNBC, and sought to identify markers of invasion in chemo-residual TNBC...
October 18, 2016: Oncotarget
Xiaoyun Dai, Kwang Seok Ahn, Ling Zhi Wang, Chulwon Kim, Amudha Deivasigamni, Frank Arfuso, Jae-Young Um, Alan Prem Kumar, Young-Chae Chang, Dhiraj Kumar, Gopal C Kundu, Junji Magae, Boon Cher Goh, Kam Man Hui, Gautam Sethi
Increasing evidence(s) have indicated that epithelial to mesenchymal transition (EMT) at the advanced stage of liver cancer, not only has the ability to self-renew and progress cancer, but also enables greater resistance to conventional chemo- and radio-therapies. Here, we report that ascochlorin (ASC), an isoprenoid antibiotic could potentiate the cytotoxic effect of doxorubicin (DOX) on HCCLM3, SNU387, SNU49, and SK-Hep-1 hepatocellular carcinoma (HCC) cells, which had a predominantly mesenchymal signature with low expression of E-cadherin but high expression of N-cadherin...
October 7, 2016: Molecular Cancer Therapeutics
Jana Jakubikova, Danka Cholujova, Teru Hideshima, Paulina Gronesova, Andrea Soltysova, Takeshi Harada, Jungnam Joo, Sun-Young Kong, Raphael E Szalat, Paul G Richardson, Nikhil C Munshi, David M Dorfman, Kenneth C Anderson
Specific niches within the tumor bone marrow (BM) microenvironment afford a sanctuary for multiple myeloma (MM) clones due to stromal cell-tumor cell interactions, which confer survival advantage and drug resistance. Defining the sequelae of tumor cell interactions within the MM niches on an individualized basis may provide the rationale for personalized therapies. To mimic the MM niche, we here describe a new 3D co-culture ex-vivo model in which primary MM patient BM cells are co-cultured with mesenchymal stem cells (MSC) in a hydrogel 3D system...
October 13, 2016: Oncotarget
Weijie Li, Shicai Dong, Wei Wei, Guangxiu Wang, Anling Zhang, Peiyu Pu, Zhifan Jia
The transcriptional coactivator with PDZ-binding motif (TAZ) is one of the important downstream effectors of Hippo pathway. In this study, the potential implication of TAZ in gliomagenesis was explored. TAZ expression was identified to be upregulated in glioma specimens and positively correlated with tumor grade. Meanwhile, its expression in nucleus was increased more significantly with the ascending order of tumor grade. Knocking down TAZ inhibited glioma cell proliferation, invasion and promoted apoptosis...
October 13, 2016: Oncotarget
Vincent Le Coz, Chaobin Zhu, Aurore Devocelle, Aimé Vazquez, Claude Boucheix, Sandy Azzi, Cindy Gallerne, Pierre Eid, Séverine Lecourt, Julien Giron-Michel
Melanoma is a particularly virulent human cancer, due to its resistance to conventional treatments and high frequency of metastasis. Melanomas contain a fraction of cells, the melanoma-initiating cells (MICs), responsible for tumor propagation and relapse. Identification of the molecular pathways supporting MICs is, therefore, vital for the development of targeted treatments. One factor produced by melanoma cells and their microenvironment, insulin-like growth factor-1 (IGF- 1), is linked to epithelial-mesenchymal transition (EMT) and stemness features in several cancers...
October 18, 2016: Oncotarget
Qiao-Li Lv, Yuan-Tao Huang, Gui-Hua Wang, Yan-Ling Liu, Jin Huang, Qiang Qu, Bao Sun, Lei Hu, Lin Cheng, Shu-Hui Chen, Hong-Hao Zhou
Emerging studies show that dysregulation of the receptor of activated protein kinase C1 (RACK1) plays a crucial role in tumorigenesis and progression of various cancers. However, the biological function and underlying mechanism of RACK1 in glioma remains poorly defined. Here, we found that RACK1 was significantly up-regulated in glioma tissues compared with normal brain tissues, being closely related to clinical stage of glioma both in mRNA and protein levels. Moreover, Kaplan-Meier analysis demonstrated that patients with high RACK1 expression had a poor prognosis (p = 0...
October 18, 2016: International Journal of Environmental Research and Public Health
Denghe Liu, Lu Sun, Xue Qin, Tianhua Liu, Shu Zhang, Yinkun Liu, Shan Li, Kun Guo
OBJECTIVE: Reprogramming energy metabolism has been defined as the ninth hallmark of cancer; glucose deprivation might be a novel, feasible and effective approach for cancer treatment. However, the comprehensive illustration of behavior alteration of hepatocellular carcinoma (HCC) cells induced by glucose restriction is lacking and associated molecular mechanism is still unclear. METHODS: Three human HCC cell lines were cultured with normal control (25.0 mM D-glucose) and low glucose (5...
September 2016: Discovery Medicine
Whitney A Greene, Teresa A Burke, Elaine D Por, Ramesh R Kaini, Heuy-Ching Wang
Purpose: The purpose of this study was to characterize the secretion profile of induced pluripotent stem cell-derived retinal pigment epithelium (iPS-RPE) during wound healing. iPS-RPE was used to develop an in vitro wound healing model. We hypothesized that iPS-RPE secretes cytokines and growth factors which act in an autocrine manner to promote migration and proliferation of cells during wound healing. Methods: iPS-RPE was grown in transwells until fully confluent and pigmented...
August 1, 2016: Investigative Ophthalmology & Visual Science
Yuan Seng Wu, Ivy Chung, Won Fen Wong, Atsushi Masamune, Maw Shin Sim, Chung Yeng Looi
BACKGROUND: We previously showed that pancreatic stellate cells (PSC) secreted interleukin (IL)-6 and promoted pancreatic ductal adenocarcinoma (PDAC) cell proliferation via nuclear factor erythroid 2 (Nrf2)-mediated metabolic reprogramming. Epithelial-mesenchymal transition (EMT) is a key process for the metastatic cascade. To study the mechanism of PDAC progression to metastasis, we investigated the role of PSC-secreted IL-6 in activating EMT and the involvement of Nrf2 in this process...
October 14, 2016: Biochimica et Biophysica Acta
Tian Lan, Lei Chang, Long Wu, Yufeng Yuan
Hepatocellular carcinoma (HCC) remains one of the most common types of cancer worldwide and prognosis remains poor. Previous studies have suggested that long non‑coding RNAs (lncRNAs) may be key regulators of tumor development and progression in HCC. It has been determined that 61‑72% of transcribed regions contain lncRNAs in the antisense orientation (aslncRNAs). However, the function of aslncRNAs in HCC remains to be elucidated. The present study investigated the function of the aslncRNA zinc finger E‑box binding homeobox 2 antisense RNA 1 (ZEB2‑AS1) in 40 HCC tissues and 5 different human HCC cell lines using reverse transcription‑quantitative polymerase chain reaction...
October 12, 2016: Molecular Medicine Reports
Mohamed Balaha, Samah Kandeel, Waleed Barakat
Carvedilol is an anti-oxidant non-selective β-blocker used for reduction of portal blood pressure, prophylaxis of esophageal varices development and bleeding in chronic liver diseases. Recently, it exhibited potent anti-inflammatory, anti-fibrotic, anti-proliferative and anti-carcinogenic effects. In the present study, we evaluated the possible suppressive effect of carvedilol on circulating and hepatic IL-6 levels responsible for hepatocarcinogenesis in a rat model of hepatic cirrhosis. Besides, its effect on hepatic STAT-3 levels, function tests, oxidative stress markers, and hydroxyproline content, hepatic tissue histopathological changes and immunohistochemical expression of E & N-cadherin...
October 13, 2016: Toxicology and Applied Pharmacology
Chih-Chin Hsu, Shiang-Fu Huang, Jong-Shyan Wang, Wing-Keung Chu, Ju-En Nien, Wei-Shan Chen, Shu-Er Chow
BACKGROUND: N-cadherin is a trans-membrane adhesion molecule associated with advanced carcinoma progression and poor prognosis. The effect of N-cadherin on matrix metalloproteinase 9 (MMP-9) regulation is implicated in human nasopharyngeal carcinoma (NPC) cell invasion. METHODS AND RESULTS: Exposure of NPC cells to phorbol-12-myristate-13-acetate (PMA) or macrophage conditioned media (CM) upregulated MMP-9 and N-cadherin cleavage, which resulted in NPC cell invasion...
October 13, 2016: BMC Cancer
Hyejung Jung, Bomin Kim, Byung In Moon, Eok-Soo Oh
During epithelial-mesenchymal transition (EMT), epithelial cells lose key phenotypic markers (e.g., E-cadherin and cytokeratin 18) and acquire mesenchymal markers (e.g., N-cadherin and vimentin). Although the loss of cytokeratin 18 is a hallmark of EMT, the regulatory role of cytokeratin 18 in EMT is not yet fully understood. Here, we report that cytokeratin 18 is involved in the regulation of transforming growth factor-beta1 (TGF-β1)-induced EMT in breast epithelial cells. When MCF10A cells were treated with TGF-β1 for 24 h, considerable morphological changes, indicative of the early stages of EMT (e...
October 13, 2016: Molecular and Cellular Biochemistry
Cuiyue Wang, Zhen Feng, Kaitong Jiang, Xiuli Zuo
Our goal was to determine the roles and regulatory mechanism of microRNA-935 (miR-935) in the progression of pancreatic cancer. The results showed that, compared with normal pancreatic tissues and cells, the expression of miR-935 was markedly upregulated while INPP4A expression was obviously downregulated in pancreatic cancer tissues and PANC-1 cells. After transfection with miR-935 inhibitor, miR-935 was significantly suppressed, and suppression of miR-935 significantly inhibited cell proliferation, suppressed cell migration, and induced cell apoptosis of pancreatic cancer cells...
October 11, 2016: Oncology Research
Junsheng Li, Barbara Kwiatkowska, Hao Lu, Maren Voglstätter, Erika Ueda, Michael Grunze, Jonathan Sleeman, Pavel A Levkin, Irina Nazarenko
Malignant transformation is associated with enhancement of cell plasticity, which allows cancer cells to survive under different conditions by adapting to their microenvironment during growth and metastatic spread. Much effort has been devoted to understanding the molecular mechanisms of these processes. Although the importance of the extracellular matrix and of surface properties in these mechanisms is evident, the direct impact of distinct physical and chemical surfaces characteristics on cell fate remains unclear...
October 12, 2016: ACS Applied Materials & Interfaces
Y Ge, Y H Lin, L A Lautscham, W H Goldmann, B Fabry, C A Naumann
Fate and function of anchorage-dependent cells depend on a variety of environmental cues, including those of mechanical nature. Previous progress in the understanding of cellular mechanosensitivity has been closely linked to the availability of artificial cell substrates of adjustable viscoelasticity, allowing for a direct correlation between substrate stiffness and cell response. Exemplary, polymeric gel substrates with polymer-conjugated cell-substrate linkers provided valuable insight into the role of mechanical signals during cell migration in an extracellular matrix environment...
October 12, 2016: Soft Matter
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