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Camille Emprou, Pauline Le Van Quyen, Jérémie Jégu, Nathalie Prim, Noëlle Weingertner, Eric Guérin, Erwan Pencreach, Michèle Legrain, Anne-Claire Voegeli, Charlotte Leduc, Bertrand Mennecier, Pierre-Emmanuel Falcoz, Anne Olland, Nicolas Santelmo, Elisabeth Quoix, Gilbert Massard, Dominique Guenot, Marie-Pierre Chenard, Michèle Beau-Faller
Lymph node metastasis is an important prognosis factor in non-small cell lung cancer (NSCLC) patients. The aim of this study was to investigate the role of epithelial to mesenchymal transition (EMT) in lymph node progression in the early stages of NSCLC. We studied a retrospective cohort of 160 consecutive surgically treated NSCLC patients with available frozen tumor samples for expression of EMT markers (CDH1, CTNNB1, CDH2, and VIMENTIN), inducers (TGFB1, c-MET, and CAIX), and transcription factors (EMT-TF: SNAI1, SNAI2, ZEB1, TWIST1, and TWIST2)...
May 29, 2018: Cancer Medicine
Meiling Tan, Caixia Liu, Wenjie Huang, Linhong Deng, Xiaoqun Qin, Yang Xiang
NEW FINDINGS: What is the central question of this study? In our previous work, CTNNAL1 (catenin alpha-like 1), an asthma-related epithelial adhesion molecule, was found to play a vital role in airway epithelial wound repair. The effect of CTNNAL1 on airway EMT has not been previously explored. What is the main finding and its importance? CTNNAL1 inhibits ozone-induced airway EMT features and mediated by repressing the expression of Twist1 mRNA and reducing TGF-β1 levels. These findings contribute to our understanding of the pathology of airway EMT and may indicate a possible therapeutic target for airway remodelling in bronchial asthma...
May 23, 2018: Experimental Physiology
Katrina L Watson, Robert A Jones, Bruce Anthony, Roger A Moorehead
The miR-200 family of microRNAs consisting of miR-141, miR-200a, miR-200b, miR-200c and miR-429 are emerging as important regulators of breast cancer progression. This family of microRNAs maintain mammary epithelial identity and downregulation of miR-200 expression has been associated with epithelial-to-mesenchymal transition in mammary tumors. Therefore, re-expression of one or more miR-200 family members in mammary tumor cells with mesenchymal characteristics may restore an epithelial phenotype including growth and metastasis suppression...
April 24, 2018: Experimental Cell Research
Laura W Bowers, Emily L Rossi, Shannon B McDonell, Steven S Doerstling, Subreen A Khatib, Claire G Lineberger, Jody E Albright, Xiaohu Tang, Linda A deGraffenried, Stephen D Hursting
Obesity is associated with poor prognosis in triple-negative breast cancer (TNBC). Preclinical models of TNBC were used to test the hypothesis that increased leptin signaling drives obesity-associated TNBC development by promoting cancer stem cell (CSC) enrichment and/or epithelial-to-mesenchymal transition (EMT). MMTV-Wnt-1 transgenic mice, which develop spontaneous basal-like, triple-negative mammary tumors, received either a control diet (10% kcal from fat) or a diet-induced obesity regimen (DIO, 60% kcal from fat) for up to 42 weeks ( n = 15/group)...
May 2018: Molecular Cancer Research: MCR
J Yamazaki, J Jelinek, S Hisamoto, A Tsukamoto, M Inaba
DNA methylation is the conversion of cytosine to 5-methylcytosine, leading to changes in the interactions between DNA and proteins. Methylation of cytosine-guanine (CpG) islands (CGIs) is associated with gene expression silencing of the involved promoter. Although studies focussing on global changes or a few single loci in DNA methylation have been performed in dogs with certain diseases, genome-wide analysis of DNA methylation is required to prospectively identify specific regions with DNA methylation change...
January 2018: Veterinary Journal
X-F Yang, G Ma, N-H Feng, D-S Yu, Y Wu, C Li
OBJECTIVE: Obesity emerged as a major public health problem worldwide, and prolonged condition with increased BMI causes various metabolic disorders include the development of kidney cancer. The metabolic changes alter the renal microenvironment and thereby promoting tumor. Hence, detailed studies of genes that regulate these this changes are keen to understand. MATERIALS AND METHODS: Initially, we successfully initiate kidney tumor using prolonged intake of a high-fat diet in Wistar rats, which are confirmed with pathological changes observed through histological sectioning...
January 2018: European Review for Medical and Pharmacological Sciences
Muhammad Mushtaq, Lasse Jensen, Sabina Davidsson, Oleksandr V Grygoruk, Ove Andrén, Vladimir Kashuba, Elena Kashuba
We have earlier found abnormal expression of the mitochondrial ribosomal protein S18-2 (MRPS18-2, S18-2) in endometrial cancer, compared to the expression in hyperplasia and in normal endometrium. Here we report that expression of S18-2 was increased with disease progression in clinical specimens of prostate cancer (PCa). The level of induction of epithelial to mesenchymal cell transition (EMT) correlated with the expression level of S18-2 in PCa cell lines. Moreover, cells acquired increased ability of migration upon S18-2 overexpression, as was evaluated in zebrafish embryo model and in trans-well assay...
February 2, 2018: Scientific Reports
Yue Hu, Liang Hu, Desheng Gong, Hanlin Lu, Yue Xuan, Ru Wang, De Wu, Daiwen Chen, Keying Zhang, Fei Gao, Lianqiang Che
Intrauterine growth restriction (IUGR) may elicit a series of postnatal body developmental and metabolic diseases due to their impaired growth and development in the mammalian embryo/fetus during pregnancy. In the present study, we hypothesized that IUGR may lead to abnormally regulated DNA methylation in the intestine, causing intestinal dysfunctions. We applied reduced representation bisulfite sequencing (RRBS) technology to study the jejunum tissues from four newborn IUGR piglets and their normal body weight (NBW) littermates...
February 1, 2018: Molecular Genetics and Genomics: MGG
Francisca Zuazo, Mirena C Astiazaran, Lourdes Rodríguez-Cabrera, Patricia Garcia-Regil, Oscar Chacon-Camacho, José L Tovilla-Canales, Juan C Zenteno
Barber-Say syndrome is a rare autosomal dominant disease characterized by dysmorphic features, mainly of the eyelids and skin. It is caused by heterozygous mutations in gene TWIST2, localized in chromosome 2q37.3. The authors present the case of a pediatric patient with a clinical diagnosis of Barber-Say syndrome with ocular symptoms related to exposure keratitis. Molecular analysis of her DNA revealed a mutation on TWIST2 gene confirming the diagnosis of Barber-Say syndrome. Surgical treatment of the patient's eyelids resolved her signs and symptoms...
March 2018: Ophthalmic Plastic and Reconstructive Surgery
Siddaraju V Boregowda, Veena Krishnappa, Jacqueline Strivelli, Christopher L Haga, Cori N Booker, Donald G Phinney
Marrow-resident mesenchymal stem cells (MSCs) serve as a functional component of the perivascular niche that regulates hematopoiesis. They also represent the main source of bone formed in adult bone marrow, and their bifurcation to osteoblast and adipocyte lineages plays a key role in skeletal homeostasis and aging. Although the tumor suppressor p53 also functions in bone organogenesis, homeostasis, and neoplasia, its role in MSCs remains poorly described. Herein, we examined the normal physiological role of p53 in primary MSCs cultured under physiologic oxygen levels...
March 2018: Cell Death and Differentiation
Wen-Fei Wei, Chen-Fei Zhou, Xiang-Guang Wu, Li-Na He, Lan-Fang Wu, Xiao-Jing Chen, Rui-Ming Yan, Mei Zhong, Yan-Hong Yu, Li Liang, Wei Wang
MicroRNAs have implicated in the relapse and metastasis of cervical cancer, which is the leading cause of cervical cancer-related mortality. However, the underlying molecular mechanisms need further elucidation. Our present study revealed that miR-221-3p is transcriptionally promoted in metastatic cervical cancer tissues compared with non-metastatic cervical cancer tissues. Forced overexpression of miR-221-3p facilitated EMT and promoted cell migration and invasion in vitro and lymphatic metastasis in vivo...
December 14, 2017: Cell Death & Disease
L Z Wang, W J Wang, Y F Xiong, S Xu, S S Wang, Y Tu, Z Y Wang, X L Yan, J H Mei, C L Wang
Objective: To investigate the significance of Twist2 in glioma and whether it is involved in the malignant transformation of glioma by epithelial-mesenchymal transition (EMT). Methods: Using immunohistochemical method detected the expression level of Twist2 in 60 cases of gliomas (including WHO grades Ⅱ, Ⅲ and Ⅳ, each for 20 cases) and 20 cases of non-tumor brain tissues. Real-time fluorescence quantitative PCR and Western blot were used to detect the expression level of Twist2 mRNA and protein in 61 cases of fresh glioma tissue (WHO grade Ⅱ 16 cases, Ⅲ 21 cases, Ⅳ 24 cases) and 12 cases of adjacent tissues, and the expression levels of E-cadherin, N-cadherin and vimentin were also investigated in fresh glioma tissue...
December 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
Yun Zhu, Wenjuan Zhang, Ping Wang
Purpose: TWIST is a critical factor for predicting prognosis in several human cancers. Here, we study the prognostic significance of TWIST1 and TWIST2 in Head and Neck squamous cell carcinoma (HNSCC) as well as interactions of TWISTs with both gender and smoking in patient survival. Methods: upper quartile normalized RNA-seq V2 RSEM values of TWIST1 and TWIST2 expressions were retrieved from a TCGA HNSCC dataset. Kaplan-Meier survival curves were used to assess the associations of TWIST1 and TWIST2 with patient survival, and multivariate Cox proportional hazards regression models were used to estimate the hazards ratios (HRs) and their 95% confidence intervals (CIs)...
October 17, 2017: Oncotarget
Bo Kou, Wei Liu, Xiaoshuang Tang, Qingshan Kou
High-mobility group AT-hook 2 (HMGA2), a member of the high mobility group family, has been reported to correlate with cancer progression. However, there is no report concerning the correlation between HMGA2 and metastasis in renal cell carcinoma. In the present study, we found that HMGA2 was highly expressed in five renal cell carcinoma cell lines compared with that in the normal renal tubular epithelial HK2 cell line. Additionally, HMGA2 facilitated cell migration and invasion of renal cell carcinoma cells, as evidenced by wound healing and Transwell assays...
January 2018: Oncology Reports
Haizea Iribar, Virginia Pérez-López, Usue Etxaniz, Araika Gutiérrez-Rivera, Ander Izeta
The embryonic origin of lineage precursors of the trunk dermis is somewhat controversial. Precursor cells traced by Myf5 and Twist2 (Dermo1) promoter activation (i.e., cells of presumed dermomyotomal lineage) have been reported to generate Schwann cells. On the other hand, abundant data demonstrate that dermal Schwann cells derive from the neural crest. This is relevant because dermal precursors give rise to neural lineages, and multilineage differentiation potential qualifies them as adult stem cells. However, it is currently unclear whether neural lineages arise from dedifferentiated Schwann cells instead of mesodermally derived dermal precursor cells...
November 14, 2017: Stem Cell Reports
Alyssa M McCoy, Jennifer L Herington, Ashley N Stouch, Anamika B Mukherjee, Omar Lakhdari, Timothy S Blackwell, Lawrence S Prince
In the immature lung, inflammation and injury disrupt the epithelial-mesenchymal interactions required for normal development. Innate immune signaling and NF-κB activation disrupt the normal expression of multiple mesenchymal genes that play a key role in airway branching and alveolar formation. To test the role of the NF-κB pathway specifically in lung mesenchyme, we utilized the mesenchymal Twist2-Cre to drive expression of a constitutively active inhibitor of NF-κB kinase subunit β (IKKβca) mutant in developing mice...
December 2017: American Journal of Pathology
Kazuki Nagashima, Shinichiro Sawa, Takeshi Nitta, Alejandro Prados, Vasiliki Koliaraki, George Kollias, Tomoki Nakashima, Hiroshi Takayanagi
The gut-associated lymphoid tissues (GALTs), including Peyer's patches (PPs), cryptopatches (CPs) and isolated lymphoid follicles (ILFs), establish a host-microbe symbiosis by the promotion of immune reactions against gut microbes. Microfold cell inducer (MCi) cells in GALTs are the recently identified mesenchymal cells that express the cytokine RANKL and initiate bacteria-specific immunoglobulin A (IgA) production via induction of microfold (M) cell differentiation. In the previous study, the Twist2-Cre driver was utilized for gene deletion in mesenchymal cells including MCi cells...
November 4, 2017: Biochemical and Biophysical Research Communications
Mohini Singh, Chitra Venugopal, Tomas Tokar, Kevin R Brown, Nicole McFarlane, David Bakhshinyan, Thusyanth Vijayakumar, Branavan Manoranjan, Sujeivan Mahendram, Parvez Vora, Maleeha Qazi, Manvir Dhillon, Amy Tong, Kathrin Durrer, Naresh Murty, Robin Hallet, John A Hassell, David R Kaplan, Jean-Claude Cutz, Igor Jurisica, Jason Moffat, Sheila K Singh
Brain metastases (BM) are the most common brain tumor in adults and are a leading cause of cancer mortality. Metastatic lesions contain subclones derived from their primary lesion, yet their functional characterization is limited by a paucity of preclinical models accurately recapitulating the metastatic cascade, emphasizing the need for a novel approach to BM and their treatment. We identified a unique subset of stem-like cells from primary human patient brain metastases, termed brain metastasis-initiating cells (BMICs)...
December 2017: Acta Neuropathologica
Ming Han, Wanpeng Xu
In this study, we aimed to explore new downstream effectors of TWIST1/2 in inducing epithelial-to-mesenchymal transition in gastric cancer. Bioinformatic data mining was performed using data in The Cancer Genome Atlas Stomach Adenocarcinoma. Survival curves were generated using Kaplan-Meier plotter. Gastric cancer cell lines (AGS and SGC-7901) were used as in vitro cell model to investigate the regulative effect of TWIST1/2 on epithelial membrane protein 3 expression and the progression of epithelial-to-mesenchymal transition...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Beatrice De Maria, Tresia de Jager, Caitlin Sarubbi, Oliver Bartsch, Alberto Bianchi, Francesco Brancati, Hon-Yin B Chung, Albert David, Ariana Kariminejad, Maura Foresti, Marina Gallottini, Bertrand Isidor, Shannon Marchegiani, Fabiana Martins, Laura Mazzanti, Nathalie Roche, Ankur Singh, Cathy Stevens, Kenichi Suga, Martin Zenker, Raoul C Hennekam
Barber-Say syndrome (BSS) and ablepharon-macrostomia syndrome (AMS) are infrequently reported congenital malformation disorders caused by mutations in the TWIST2 gene. Both are characterized by abnormalities in ectoderm-derived structures and cause a very unusual morphology of mainly the face in individuals with otherwise normal cognition and normal physical functioning. We studied the impact that the presence of BSS and AMS has on psychosocial functioning of affected individuals and their families, using their point of view to start with...
June 2017: Molecular Syndromology
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