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https://www.readbyqxmd.com/read/28198361/dub3-inhibition-suppresses-breast-cancer-invasion-and-metastasis-by-promoting-snail1-degradation
#1
Yadi Wu, Yu Wang, Yiwei Lin, Yajuan Liu, Yifan Wang, Jianhang Jia, Puja Singh, Young-In Chi, Chi Wang, Chenfang Dong, Wei Li, Min Tao, Dana Napier, Qiuying Shi, Jiong Deng, B Mark Evers, Binhua P Zhou
Snail1, a key transcription factor of epithelial-mesenchymal transition (EMT), is subjected to ubiquitination and degradation, but the mechanism by which Snail1 is stabilized in tumours remains unclear. We identify Dub3 as a bona fide Snail1 deubiquitinase, which interacts with and stabilizes Snail1. Dub3 is overexpressed in breast cancer; knockdown of Dub3 resulted in Snail1 destabilization, suppressed EMT and decreased tumour cell migration, invasion, and metastasis. These effects are rescued by ectopic Snail1 expression...
February 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28186089/adenovirus-mediated-tipe2-overexpression-inhibits-gastric-cancer-metastasis-via-reversal-of-epithelial-mesenchymal-transition
#2
H Yin, X Huang, M Tao, Q Hu, J Qiu, W Chen, J Wu, Y Xie
Tumor necrosis factor (TNF)-alpha-induced protein 8-like 2 (TNFAIP8L2; also termed TIPE2) has been shown to be involved in both the immune-negative modulation and cancer. We previously found that TIPE2 is lost in human gastric cancer, and TIPE2 restoration suppresses gastric cancer growth by induction of apoptosis and impairment of protein kinase B (PKB/AKT) and extracellular signal-regulated kinase-1/2 (ERK1/2) signaling. However, its correlation with epithelial-mesenchymal transition (EMT) in gastric cancer is largely elusive...
February 10, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28177668/chimaphilin-inhibits-human-osteosarcoma-cells-invasion-and-metastasis-through-suppressing-the-tgf-%C3%AE-1-induced-epithelial-to-mesenchymal-transition-markers-via-pi-3k-akt-erk1-2-and-smad-signaling-pathways
#3
Feng Dong, Tingting Liu, Hao Jin, Wenbo Wang
Epithelial-to-mesenchymal transition is a cellular process associated with cancer invasion and metastasis. However, the anti-metastatic effects of chimaphilin remain elusive. In this study, we attempted to investigate the potential use of chimaphilin as an inhibitor of TGF-β1-induced epithelial-to-mesenchymal in U2OS cells. We found that TGF-β1 induced epithelial-to-mesenchymal to promote U2OS cells invasion and metastasis. Western blotting demonstrated that chimaphilin inhibited U2OS cells invasion and migration, increased the expression of the epithelial phenotype marker E-cadherin, repressed the expression of the mesenchymal phenotype marker Vimentin, as well as decreased the level of epithelial-to-mesenchymal-inducing transcription factors Snail1 and Slug during the initiation of TGF-β1-induced epithelial-to-mesenchymal...
January 29, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28145431/mir-34a-inhibits-pancreatic-cancer-progression-through-snail1-mediated-epithelial-mesenchymal-transition-and-the-notch-signaling-pathway
#4
Yan Tang, Yong Tang, Ying-Sheng Cheng
Epithelial-mesenchymal transition (EMT) and Notch signaling are important for the growth and invasion of pancreatic cancer, which is a leading cause of cancer-related deaths worldwide. miR-34a has been shown to play pivotal roles in the progression of several types of cancer. However, little is known about the regulatory mechanisms of miR-34a in pancreatic cancer processes. The aim of this study was to determine whether miR-34a has negative effects on pancreatic cancer and whether these effects are related to EMT and Notch signaling...
February 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28135249/the-cdc42-rac1-regulator-cdgap-is-a-novel-e-cadherin-transcriptional-co-repressor-with-zeb2-in-breast-cancer
#5
Y He, J J Northey, A Pelletier, Z Kos, L Meunier, B Haibe-Kains, A-M Mes-Masson, J-F Côté, P M Siegel, N Lamarche-Vane
The loss of E-cadherin causes dysfunction of the cell-cell junction machinery, which is an initial step in epithelial-to-mesenchymal transition (EMT), facilitating cancer cell invasion and the formation of metastases. A set of transcriptional repressors of E-cadherin (CDH1) gene expression, including Snail1, Snail2 and Zeb2 mediate E-cadherin downregulation in breast cancer. However, the molecular mechanisms underlying the control of E-cadherin expression in breast cancer progression remain largely unknown...
January 30, 2017: Oncogene
https://www.readbyqxmd.com/read/28127848/mir-30c-protects-diabetic-nephropathy-by-suppressing-epithelial-to-mesenchymal-transition-in-db-db-mice
#6
Yanru Zhao, Zhongwei Yin, Huaping Li, Jiahui Fan, Shenglan Yang, Chen Chen, Dao Wen Wang
Epithelial-to-mesenchymal transition (EMT) plays a significant role in tubulointerstitial fibrosis, which is a hallmark of diabetic nephropathy. Thus, identifying the mechanisms of EMT activation could be meaningful. In this study, loss of miR-30c accompanied with increased EMT was observed in renal tubules of db/db mice and cultured HK2 cells exposed to high glucose. To further explore the roles of miR-30c in EMT and tubulointerstitial fibrosis, recombinant adeno-associated viral vector was applied to manipulate the expression of miR-30c...
January 27, 2017: Aging Cell
https://www.readbyqxmd.com/read/28125654/human-deciduous-teeth-stem-cells-shed-display-neural-crest-signature-characters
#7
Karlen G Gazarian, Luis R Ramírez-García
Human dental tissues are sources of neural crest origin multipotent stem cells whose regenerative potential is a focus of extensive studies. Rational programming of clinical applications requires a more detailed knowledge of the characters inherited from neural crest. Investigation of neural crest cells generated from human pluripotent stem cells provided opportunity for their comparison with the postnatal dental cells. The purpose of this study was to investigate the role of the culture conditions in the expression by dental cells of neural crest characters...
2017: PloS One
https://www.readbyqxmd.com/read/28100026/mir-203-inhibits-augmented-proliferation-and-metastasis-of-hepatocellular-carcinoma-residual-in-the-promoted-regenerating-liver
#8
Xiao-Bo Zheng, Xiao-Bo Chen, Liang-Liang Xu, Ming Zhang, Lei Feng, Peng-Sheng Yi, Jian-Wei Tang, Ming-Qing Xu
Liver resection is still the most commonly used therapeutic option for hepatocellular carcinoma (HCC) at present, and liver regeneration promotes HCC growth in the regenerating liver. The higher recurrence/metastasis of HCC is the main cause of death for HCC patients after liver resection. However, it remains unclear how to abolish the augmented growth and metastasis of the possible residual HCC induced by the promoted liver regeneration after liver resection. In this study, a rat model with liver cirrhosis and diffused HCC was established by Diethylnitrosamine administration, recombinant miR-203 adenovirus was administered to induce hepatic miR-203 overexpression and 30% partial hepatectomy (PH) was followed, then the effect of miR-203 on the proliferation, invasion and metastasis of the residual HCC in the remnant cirrhotic liver with promoted regeneration was investigated...
January 18, 2017: Cancer Science
https://www.readbyqxmd.com/read/28098914/role-of-mir-647-in-human-gastric-cancer-suppression
#9
Wenlong Cao, Weiyuan Wei, Zexu Zhan, Dongyi Xie, Yubo Xie, Qiang Xiao
MicroRNAs (miRNAs) regulate various oncogenes concomitantly, resulting in tumor suppression. They regulate proliferation and migration pathways in tumor development, suggesting a potential therapeutic role. In the present study, we found that miR-647 was markedly downregulated in gastric cancer (GC), and was significantly correlated with reduced tumor size and metastasis. In addition, miR-647 was also reduced in GC cell lines. Furthermore, overexpression of miR-647 in the GC cell lines inhibited cell proliferation, promoted cell cycle arrest at the G0/G1 phase and induced cell apoptosis...
January 17, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28093067/capza1-modulates-emt-by-regulating-actin-cytoskeleton-remodelling-in-hepatocellular-carcinoma
#10
Deng Huang, Li Cao, Shuguo Zheng
BACKGROUND: Epithelial-mesenchymal transition (EMT) elicits dramatic changes, including cytoskeleton remodelling as well as changes in gene expression and cellular phenotypes. During this process, actin filament assembly plays an important role in maintaining the morphology and movement of tumour cells. Capping protein, a protein complex referred to as CapZ, is an actin-binding complex that can regulate actin cytoskeleton remodelling. CAPZA1 is the α1 subunit of this complex, and we hypothesized that CAPZA1 regulates EMT through the regulation of actin filaments assembly, thus reducing the metastatic ability of hepatocellular carcinoma (HCC) cells...
January 16, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28087626/snail2-and-zeb2-repress-p-cadherin-to-define-embryonic-territories-in-the-chick-embryo
#11
Hervé Acloque, Oscar H Ocaña, Diana Abad, Claudio D Stern, M Angela Nieto
Snail and Zeb transcription factors induce epithelial to mesenchymal transition (EMT) in embryonic and adult tissues by direct repression of E-Cadherin transcription. The repression of E-Cadherin transcription by the EMT inducers Snail1 and Zeb2 plays a fundamental role in defining embryonic territories in the mouse, as E-Cadherin needs to be downregulated in the primitive streak and in the epiblast concomitant with the formation of mesendodermal precursors and the neural plate, respectively. Here we show that in the chick embryo, E-Cadherin is weakly expressed in the epiblast at pre-primitive streak stages where it is substituted by P-Cadherin We also show that Snail2 and Zeb2 repress P-Cadherin transcription in the primitive streak and the neural plate, respectively...
January 13, 2017: Development
https://www.readbyqxmd.com/read/28081224/resveratrol-impairs-glioma-stem-cells-proliferation-and-motility-by-modulating-the-wnt-signaling-pathway
#12
Chiara Cilibrasi, Gabriele Riva, Gabriele Romano, Massimiliano Cadamuro, Riccardo Bazzoni, Valentina Butta, Laura Paoletta, Leda Dalprà, Mario Strazzabosco, Marialuisa Lavitrano, Roberto Giovannoni, Angela Bentivegna
Glioblastoma multiforme (GBM) is a grade IV astrocytoma and the most common form of malignant brain tumor in adults. GBM remains one of the most fatal and least successfully treated solid tumors: current therapies provide a median survival of 12-15 months after diagnosis, due to the high recurrence rate. Glioma Stem Cells (GSCs) are believed to be the real driving force of tumor initiation, progression and relapse. Therefore, better therapeutic strategies GSCs-targeted are needed. Resveratrol is a polyphenolic phytoalexin found in fruits and vegetables displaying pleiotropic health benefits...
2017: PloS One
https://www.readbyqxmd.com/read/28067227/cdk4-6-dependent-activation-of-dub3-regulates-cancer-metastasis-through-snail1
#13
Tongzheng Liu, Jia Yu, Min Deng, Yujiao Yin, Haoxing Zhang, Kuntian Luo, Bo Qin, Yunhui Li, Chenming Wu, Tao Ren, Yang Han, Peng Yin, JungJin Kim, SeungBaek Lee, Jing Lin, Lizhi Zhang, Jun Zhang, Somaira Nowsheen, Liewei Wang, Judy Boughey, Matthew P Goetz, Jian Yuan, Zhenkun Lou
Tumour metastasis, the spread of cancer cells from the original tumour site followed by growth of secondary tumours at distant organs, is the primary cause of cancer-related deaths and remains poorly understood. Here we demonstrate that inhibition of CDK4/6 blocks breast tumour metastasis in the triple-negative breast cancer model, without affecting tumour growth. Mechanistically, we identify a deubiquitinase, DUB3, as a target of CDK4/6; CDK4/6-mediated activation of DUB3 is essential to deubiquitinate and stabilize SNAIL1, a key factor promoting epithelial-mesenchymal transition and breast cancer metastasis...
January 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28062404/endothelial-to-mesenchymal-transition-contributes-to-endothelial-dysfunction-and-dermal-fibrosis-in-systemic-sclerosis
#14
Mirko Manetti, Eloisa Romano, Irene Rosa, Serena Guiducci, Silvia Bellando-Randone, Amato De Paulis, Lidia Ibba-Manneschi, Marco Matucci-Cerinic
OBJECTIVE: Systemic sclerosis (SSc) features multiorgan fibrosis orchestrated predominantly by activated myofibroblasts. Endothelial-to-mesenchymal transition (EndoMT) is a transdifferentiation by which endothelial cells (ECs) lose their specific morphology/markers and acquire myofibroblast-like features. Here, we determined the possible contribution of EndoMT to the pathogenesis of dermal fibrosis in SSc and two mouse models. METHODS: Skin sections were immunostained for endothelial CD31 or vascular endothelial (VE)-cadherin in combination with α-smooth muscle actin (α-SMA) myofibroblast marker...
January 6, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28057716/mir-211-5p-suppresses-metastatic-behavior-by-targeting-snai1-in-renal-cancer
#15
Kefeng Wang, Wei Jin, Peng Jin, Xiang Fei, Xia Wang, Xiaonan Chen
: The snail family transcriptional repressor 1 (SNAI1) is known to promote metastatic phenotypes in renal cell carcinoma (RCC). However, the mechanism by which SNAI1 promotes RCC metastasis remains largely unexplored. Here, bioinformatics and quantitative validation revealed that miR-211-5p was downregulated in metastatic RCC clinical specimens compared to non-metastatic RCC tissues. Overexpression of miR-211-5p suppressed RCC cell migration and invasion via downregulation of SNAI1 expression...
January 5, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28032372/microrna-210-is-increased-and-it-is-required-for-dedifferentiation-of-osteosarcoma-cell-line
#16
Haixia Zhang, Qing Mai, Juntao Chen
Osteosarcoma (OS) is the most common malignant bone tumor and is prevalent in adolescents. In clinical studies, miR-210 has been reported to be tightly correlated to the poor prognosis of OS. Nevertheless, its roles in OS have not been fully elucidated. In view of the central role played by OS stem cells (OSCs) in the malignant progression of OS, this study investigated the influence of miR-210 on the formation of OSCs. Our previous findings suggested that the microenvironment of bone, abundant TGF-β1 and hypoxia, could induce OS cells to dedifferentiate into OSCs...
March 2017: Cell Biology International
https://www.readbyqxmd.com/read/27966519/combretastatin-a4-regulates-proliferation-migration-invasion-and-apoptosis-of-thyroid-cancer-cells-via-pi3k-akt-signaling-pathway
#17
Weixin Liang, Yongqiang Lai, Mingzhang Zhu, Shangshu Huang, Weizhao Feng, Xiaoyu Gu
BACKGROUND Combretastatin A4 (CA4) is a potential therapeutic candidate for a variety of human cancer treatments. However, the inhibitive effects of CA4 on thyroid cancer cells are still not well-clarified. This study aimed to investigate the potential effect of CA4 on thyroid cancer cells, as well as underlying mechanism. MATERIAL AND METHODS Human thyroid papillary carcinoma cell line TPC1 was pre-treated with 5 concentrations of CA4 (0, 1, 2, 5, or 10 μM) for 2 h. Cell proliferation was determined by 3-(4, 5-dimethyl-2- thiazolyl)-2, 5-diphenyl -2-H-tetrazolium bromide (MTT) assay...
December 14, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27936102/am251-suppresses-epithelial-mesenchymal-transition-of-renal-tubular-epithelial-cells
#18
Tomoyo Yoshinaga, Kenichiro Uwabe, Shoichi Naito, Kenichi Higashino, Toru Nakano, Yoshito Numata, Akio Kihara
Epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells is one of the causative mechanisms of kidney fibrosis. In our study, we screened lipophilic compounds using a lipid library including approximately 200 lipids to identify those that suppressed EMT induced by a transforming growth factor (TGF)-β1 stimulus. Initial screening was performed with the immortalized HK-2 renal tubule epithelial cell line. The most promising compounds were further tested in RPTEC primary renal tubule epithelial cells...
2016: PloS One
https://www.readbyqxmd.com/read/27923654/zeb1-is-neither-sufficient-nor-required-for-epithelial-mesenchymal-transition-in-ls174t-colorectal-cancer-cells
#19
Sabine Jägle, Annika Dertmann, Monika Schrempp, Andreas Hecht
Epithelial-mesenchymal transition (EMT) is implicated in metastases formation and acquired therapy resistance in several tumor entities. The two transcription factors SNAIL1 and ZEB1 are thought to be master regulators of EMT and to form a core regulatory network required for EMT-associated transcriptional reprogramming. Yet, inducible EMT models show the sequential upregulation first of SNAIL1 and only subsequently of ZEB1. Therefore, SNAIL1 and ZEB1 might be differentially needed for the onset and propagation of EMT...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27916370/tanshinone-iia-attenuates-epithelial-mesenchymal-transition-to-inhibit-the-tracheal-narrowing
#20
Hongtao Duan, Lijie Ma, Honggang Liu, Yong Zhang, Zhipei Zhang, Xiaolong Yan, Xiaofei Li
BACKGROUND: This study examines the effects of tanshinone IIA (TIIA) on epithelial-mesenchymal transition (EMT) in tracheal transplantation and the ability of TIIA to inhibit tracheal narrowing after tracheal transplantation. Mechanisms that may be involved in this process are also explored. METHODS: Human bronchial epithelial cells were treated in vitro with TGF-β1 for 72 h. The cells were pretreated with TIIA (40 μg/mL) or DMSO for 2 h before TGF-β1 stimulation...
November 2016: Journal of Surgical Research
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