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Thomas Bonacci, Michael J Emanuele
The Anaphase-Promoting Complex/Cyclosome (APC/C) is an E3 ubiquitin ligase and key regulator of cell cycle progression. By triggering the degradation of mitotic cyclins, APC/C controls cell cycle-dependent oscillations in Cyclin Dependent Kinase (CDK) activity. Thus, the dynamic activities of both APC/C and CDK sit at the core of the cell cycle oscillator. The APC/C controls a large number of substrates and is regulated through multiple mechanisms, including cofactor-dependent activation. These cofactors, Cdc20 and Cdh1, recognize substrates, while the specific E2 enzymes UBE2C/UbcH10 and UBE2S cooperate with APC/C to build K11-linked ubiquitin chains on substrates to target them for proteasomal degradation...
March 15, 2019: Cell Cycle
Sadhika Sood, Gladell P Paner
Plasmacytoid urothelial carcinoma (PUC) is a variant of infiltrating urothelial carcinoma that is characterized by tumor cells that have striking morphologic resemblance to and immunohistochemical overlap with plasma cells, and that harbors CDH1 mutation. Plasmacytoid urothelial carcinoma can be widely infiltrative and may permeate the urinary bladder in a linitis plastica-like manner and spread along the fascial planes and into the peritoneum. Compared with conventional urothelial carcinoma, PUCs have greater chance for higher-stage disease, surgical margin positivity, and metastasis at presentation that translate into its poorer outcome...
March 13, 2019: Archives of Pathology & Laboratory Medicine
Xiaojing Zhang, Wei Chen, Ning Yin, Lijia Dong, Ming Fu, Qimin Zhan, Tong Tong
Overexpressed in lung cancer 1 (OLC1) is a potential oncogene overexpressed in human lung cancer and in other types of malignant tumor. The elevated expression of OLC1 contributes to tumor genesis and progression. However, the mechanisms regulating the expression of OLC1 remain unclear. In the present study, using lung and esophageal cancer cell lines, it was demonstrated that OLC1 was a short-lived, cell cycle-dependent protein regulated through the anaphase-promoting complex/cyclosome (APC/c)-ubiquitin pathway by directly interacting with the APC2 subunit...
March 2019: Oncology Letters
Kristyna Pivovarcikova, Abbas Agaimy, Petr Martinek, Reza Alaghehbandan, Delia Perez Montiel, Isabel Alvarado Cabrero, Joanna Rogala, Naoto Kuroda, Boris Rychly, Slavko Gasparov, Kvetoslava Michalova, Michal Michal, Milan Hora, Tomas Pitra, Inna Tuckova, Simon Laciok, Jana Mareckova, Ondrej Hes
AIMS: Primary renal well-differentiated neuroendocrine tumor (hereafter referred to as renal NET) is rare, with approximately 100 cases reported in the literature. There is also limited data available on the molecular genetic background of primary renal NETs. METHODS: We analyzed 11 renal NETs using next generation sequencing (NGS) to identify characteristic genetic aberrations. RESULTS: All tumors were positive for synaptophysin and expressed in addition INSM-1 (10/11), chromogranin-A (8/11), and CD56 (3/11)...
March 9, 2019: Histopathology
Rui Hu, Huawei Zou, Zhisheng Wang, Binghai Cao, Quanhui Peng, Xiaoping Jing, Yixin Wang, Yaqun Shao, Zhaoxi Pei, Xiangfei Zhang, Bai Xue, Lizhi Wang, Suonan Zhao, Yuqing Zhou, Xiangying Kong
Growth retardation reduces the incomes of livestock farming. However, effective nutritional interventions to promote compensatory growth and the mechanisms involving digestive tract microbiomes and transcripts have yet to be elucidated. In this study, Qinghai plateau yaks, which frequently suffer from growth retardation due to malnutrition, were used as an experimental model. Young growth-retarded yaks were pastured (GRP), fed basal ration (GRB), fed basal ration addition cysteamine hydrochloride (CSH; GRBC) or active dry yeast (ADY; GRBY)...
2019: Frontiers in Microbiology
Fatemeh Shokraii, Maryam Moharrami, Nasrin Motamed, Maryam Shahhoseini, Mehdi Totonchi, Vahid Ezzatizadeh, Javad Firouzi, Pardis Khosravani, Marzieh Ebrahimi
Objective: Cadherin-1 ( CDH1 ) plays an important role in the metastasis, while expression of this protein is under control of epigenetic changes on its gene promoter. Therefore we evaluated both DNA methylation (DNAmet) and histone modification marks of CDH1 in prostate cancer stem like cells (PCSLCs). Materials and Methods: In this experimental study, we isolated PCSLCs using cell surface marker and prostaspheroid formation, respectively. The cells isolated from both methods were characterized and then the levels of H3K4me2, H3K27me3, H3K9me2/3 and H3K9ac as well as DNAmet were assessed in CDH1 promoter of the isolated cells...
July 2019: Cell Journal
Miyako Kurihara-Shimomura, Tomonori Sasahira, Hiroyuki Shimomura, Chie Nakashima, Tadaaki Kirita
BACKGROUND: The relationship between miR-29b-1-5p and c-Met proto-oncogene in oral squamous cell carcinoma (OSCC) remains to be investigated. This study aimed to reveal the role of miR-29b-1-5p in the pathogenesis of OSCC using molecular and biological analyses. METHODS: We investigated the expression of miR-29b-1-5p , c-Met, and markers of the epithelial-mesenchymal transition (EMT) in the tissues of 49 patients with OSCC and in human OSCC cells with different tumorigenicity...
February 24, 2019: Journal of Clinical Medicine
JeongGoo Lee, Eric Jung, Martin Heur
Purpose: To determine whether the mouse corneal endothelium enters endothelial to mesenchymal transition (EndoMT) following surgical injury in vivo. Methods: The corneal endothelium in anesthetized mice was surgically injured in vivo under direct visualization. The secretion of interleukin-1 beta (IL-1β) and fibroblast growth factor 2 (FGF2) into the aqueous humor was analyzed with western blotting. The expression of FGF2 , Snai1 , Zeb1 , Col1a1 , Col1a2 , Fn1 , Vim , Cdk2 , Ccne1 , and Cdh1 was analyzed with semiquantitative RT-PCR in the mouse corneal endothelium ex vivo and in vivo...
2019: Molecular Vision
Junhun Cho, Soomin Ahn, Dae-Soon Son, Nayoung Kd Kim, Ki-Wook Lee, Seungtae Kim, Jeeyun Lee, Se Hoon Park, Joon Oh Park, Won Ki Kang, Ji Yeong An, Min Gew Choi, Jun-Ho Lee, Tae Sung Sohn, Jae Moon Bae, Sung Kim, Kyoung-Mee Kim
Genetic alterations are the starting point leading to numerous changes in clinical and pathologic features (phenotypes) of individual cancers; however, their inter-relationships in gastric cancers (GC) are unclear. We performed massive parallel sequencing of 381 cancer-related genes and compared the results with clinical and pathologic findings in 330 GC. High tumor mutation burden (TMB) accounted for 11% of GC (n=37) and all 19 MSI-H GCs were high TMB. High TMB was significantly more frequent in intestinal-type by Lauren, tumor with higher host cellular immune response, earlier AJCC stage, and favorable prognosis...
February 23, 2019: International Journal of Cancer. Journal International du Cancer
Jie Wang, Peng Lei, Amr Ahmed Abdelrahim Gamil, Leidy Lagos, Yang Yue, Kristin Schirmer, Liv Torunn Mydland, Margareth Øverland, Åshild Krogdahl, Trond M Kortner
The objective of this study was to evaluate the suitability of the rainbow trout intestinal epithelial cell line (RTgutGC) as an in vitro model for studies of gut immune function and effects of functional feed ingredients. Effects of lipopolysaccharide (LPS) and three functional feed ingredients [nucleotides, mannanoligosaccharides (MOS), and beta-glucans] were evaluated in RTgutGC cells grown on conventional culture plates and transwell membranes. Permeation of fluorescently-labeled albumin, transepithelial electrical resistance (TEER), and tight junction protein expression confirmed the barrier function of the cells...
2019: Frontiers in Immunology
Yihua Wang, Hua Xiong, Dian Liu, Charlotte Hill, Ayse Ertay, Juanjuan Li, Yanmei Zou, Paul Miller, Eileen White, Julian Downward, Robert D Goldin, Xianglin Yuan, Xin Lu
Macroautophagy/autophagy inhibition is a novel anticancer therapeutic strategy, especially for tumors driven by mutant RAS. Here, we demonstrate that autophagy inhibition in RAS-mutated cells induces epithelial-mesenchymal transition (EMT), which is associated with enhanced tumor invasion. This is at least partially achieved by triggering the NFKB/NF-κB pathway via SQSTM1/p62. Knockdown of ATG3 or ATG5 increases oncogenic RAS-induced expression of ZEB1 and SNAI2/Snail2, and activates NFKB activity. Depletion of SQSTM1 abolishes the activation of the NFKB pathway induced by autophagy inhibition in RAS-mutated cells...
February 20, 2019: Autophagy
Darrell Andrews, Giorgio Oliviero, Letizia De Chiara, Ariane Watson, Emily Rochford, Kieran Wynne, Ciaran Kennedy, Shane Clerkin, Benjamin Doyle, Catherine Godson, Paul Connell, Colm O'Brien, Gerard Cagney, John Crean
Cell differentiation is directed by extracellular cues and intrinsic epigenetic modifications, which control chromatin organization and transcriptional activation. Central to this process is PRC2, which modulates the di- and trimethylation of lysine 27 on histone 3; however, little is known concerning the direction of PRC2 to specific loci. Here, we have investigated the physical interactome of EZH2, the enzymatic core of PRC2, during retinoic acid-mediated differentiation of neuroepithelial, pluripotent NT2 cells and the dedifferentiation of neuroretinal epithelial ARPE19 cells in response to TGF-β...
February 19, 2019: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Alec J McCann, Tina L Samuels, Joel H Blumin, Nikki Johnston
OBJECTIVES: Idiopathic subglottic stenosis (iSGS) is commonly characterized by laryngeal fibrosis thought to arise by epithelia-mesenchymal transition (EMT) induced by chronic inflammation. Pepsin is a potent inducer of inflammation in the airways during chronic laryngopharyngeal reflux and has been observed in the subglottic mucosa of patients with iSGS, absent in normal mucosa. The aim of this study was to examine the effect of pepsin on mechanisms of EMT in laryngeal cells with implications for iSGS...
February 18, 2019: Laryngoscope
Bastien Nguyen, David Venet, Matteo Lambertini, Christine Desmedt, Roberto Salgado, Hugo Mark Horlings, Françoise Rothé, Christos Sotiriou
BACKGROUND: Although parity and age at first pregnancy are among the most known extrinsic factors that modulate breast cancer risk, their impact on the biology of subsequent breast cancer has never been explored in depth. Recent data suggest that pregnancy-induced tumor protection is different according to breast cancer subtypes, with parity and young age at first pregnancy being associated with a marked reduction in the risk of developing luminal subtype but not triple negative breast cancer...
February 15, 2019: Breast Cancer Research: BCR
Lea A Rempel, Megan M Krautkramer, John J Parrish, Jeremy R Miles
Epigenetics includes the study of external factors that can influence the expression of genes by altering the accessibility of DNA through methylation. To investigate the epigenetic influence of season, sperm head shape, and semen storage on placental and fetal tissues, pregnancies were generated in the summer or winter using boar semen from either least or most sperm head shape change, collected during cool or warm seasons, and stored as cooled-extended or cryopreserved. The lowest (p < 0.05) ratios of 5-methylcytosine to 5-hydroxymethylcytosine activity (5mC:5hmC) in fetal liver were from summer breedings and in placental tissues from winter breedings...
February 14, 2019: Molecular Reproduction and Development
Mansour Alsaleem, Michael S Toss, Chitra Joseph, Mohammed Aleskandarany, Sasagu Kurozumi, Ibrahim Alshankyty, Angela Ogden, Padmashree C G Rida, Ian O Ellis, Ritu Aneja, Andrew R Green, Nigel P Mongan, Emad A Rakha
E-cadherin is a tumor suppressor gene in invasive lobular breast cancer. However, a proportion of high-grade ductal carcinoma shows reduced/loss of E-cadherin. In this study, we assessed the underlying mechanisms and molecular implications of E-cadherin loss in invasive ductal carcinoma. This study used large, well-characterized cohorts of early-stage breast cancer-evaluated E-cadherin expression via various platforms including immunohistochemistry, microarray analysis using Illumina HT-12 v3, copy number analysis using Affymetrix SNP 6...
February 13, 2019: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Laurence Finot, Eric Chanat, Frederic Dessauge
Milk production is highly dependent on the optimal development of the mammary epithelium. It is therefore essential to better understand mammary epithelial cell growth and maintenance from the related epithelial lineage during the animal life. Here, we characterized the epithelial lineage at puberty, lactation and dry-off in bovine using the cell surface markers CD49f , CD24, and CD10. The pubertal period was characterized by a high proportion of CD49f pos cells corresponding to various epithelial subpopulations, notably the CD24pos subpopulations...
February 13, 2019: Journal of Mammary Gland Biology and Neoplasia
Winifred Lo, Bin Zhu, Arvind Sabesan, Ho-Hsiang Wu, Astin Powers, Rebecca A Sorber, Sarangan Ravichandran, Ina Chen, Lucas A McDuffie, Humair S Quadri, Joal D Beane, Kathleen Calzone, Markku M Miettinen, Stephen M Hewitt, Christopher Koh, Theo Heller, Sholom Wacholder, Udo Rudloff
INTRODUCTION: Hereditary diffuse gastric cancer (HDGC) is a cancer syndrome associated with variants in E-cadherin (CDH1), diffuse gastric cancer and lobular breast cancer. There is considerable heterogeneity in its clinical manifestations. This study aimed to determine associations between CDH1 germline variant status and clinical phenotypes of HDGC. METHODS: One hundred and fifty-two HDGC families, including six previously unreported families, were identified...
February 11, 2019: Journal of Medical Genetics
Bin Liu, Wenjie Bai, Guoyao Ou, Jun Zhang
Cdh1 is a regulatory subunit of the anaphase promoting complex/cyclosome (APC/C), known to be involved in regulating neuronal survival. The role of Cdh1 in volatile anesthetics-induced neuronal apoptosis in the developing brain is unknown. In this study, we used postnatal day 7 (P7) and day 21 (P21) mice exposed to 2.3% sevoflurane for 6 h to investigate at which age and duration of exposure sevoflurane affects the expression of Cdh1 and glycolytic enzyme 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) and that of the pentose phosphate pathway (PPP) enzyme, Glucose-6-phosphate dehydrogenase (G6PD)...
February 11, 2019: ACS Chemical Neuroscience
Bailey A Koch, Hui Jin, Robert J Tomko, Hong-Guo Yu
The nucleus is enclosed by the inner nuclear membrane (INM) and the outer nuclear membrane (ONM). While the ONM is continuous with the endoplasmic reticulum (ER), the INM is independent and separates the nucleoplasm from the ER lumen. Turnover of ER proteins has been well characterized by the ER-associated protein degradation (ERAD) pathway, but very little is known about turnover of resident INM proteins. Here we show that the anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase, regulates the degradation of Mps3, a conserved integral protein of the INM...
February 8, 2019: Journal of Cell Biology
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