scholarly journals Drosophila Neuroblast Selection Gated by Notch, Snail, SoxB and EMT Gene Interplay

2019 ◽  
Author(s):  
Badrul Arefin ◽  
Farjana Parvin ◽  
Shahrzad Bahrampour ◽  
Caroline Bivik Stadler ◽  
Stefan Thor
Keyword(s):  
Lateral Inhibition ◽  
Epithelial Mesenchymal Transition ◽  
Notch Pathway ◽  
Evolutionary Conservation ◽  
Neural Progenitor ◽  
Notch Signalling ◽  
Proneural Genes ◽  
Mesenchymal Transition ◽  
Soxb Gene ◽  
Snail Gene

SUMMARYIn the developing Drosophila central nervous system neural progenitor (neuroblast; NB) selection is gated by lateral inhibition, controlled by Notch signalling and proneural genes. However, proneural mutants only display partial NB reduction, indicating the existence of additional genes with proneural activity. In addition, recent studies reveal involvement of key epithelial-mesenchymal transition (EMT) genes in NB selection, but the regulatory interplay between Notch signalling and the EMT machinery is unclear. We find that the SoxB gene SoxNeuro and the Snail gene worniou are integrated with the Notch pathway, and constitute the missing proneural genes. Notch signalling, the proneural, SoxNeuro, and worniou genes regulate key EMT genes to orchestrate the NB specification process. Hence, we uncover an expanded lateral inhibition network for NB specification, and demonstrate its link to key players in the EMT machinery. Because of the evolutionary conservation of the genes involved, the Notch-SoxB-Snail-EMT network may control neural progenitor selection in many other systems.

LncRNA Meg8 suppresses activation of hepatic stellate cells and epithelial-mesenchymal transition of hepatocytes via the Notch pathway

2020 ◽  
Vol 521 (4) ◽  
pp. 921-927 ◽  
Author(s):  
Ting Chen ◽  
Huajiang Lin ◽  
Xun Chen ◽  
Guantong Li ◽  
Yanmian Zhao ◽  
...  
Keyword(s):  
Hepatic Stellate Cells ◽  
Epithelial Mesenchymal Transition ◽  
Notch Pathway ◽  
Stellate Cells ◽  
Mesenchymal Transition

scholarly journals MicroRNA-26a and -26b inhibit lens fibrosis and cataract by negatively regulating Jagged-1/Notch signaling pathway

2017 ◽  
Vol 24 (8) ◽  
pp. 1431-1442 ◽  
Author(s):  
Xiaoyun Chen ◽  
Wei Xiao ◽  
Weirong Chen ◽  
Xialin Liu ◽  
Mingxing Wu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Notch Signaling ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Notch Pathway ◽  
Lens Epithelial Cells ◽  
Mesenchymal Transition ◽  
Fibrotic Diseases

Abstract Fibrosis is a chronic process involving development and progression of multiple diseases in various organs and is responsible for almost half of all known deaths. Epithelial–mesenchymal transition (EMT) is the vital process in organ fibrosis. Lens is an elegant biological tool to investigate the fibrosis process because of its unique biological properties. Using gain- and loss-of-function assays, and different lens fibrosis models, here we demonstrated that microRNA (miR)-26a and miR-26b, members of the miR-26 family have key roles in EMT and fibrosis. They can significantly inhibit proliferation, migration, EMT of lens epithelial cells and lens fibrosis in vitro and in vivo. Interestingly, we revealed that the mechanisms of anti-EMT effects of miR-26a and -26b are via directly targeting Jagged-1 and suppressing Jagged-1/Notch signaling. Furthermore, we provided in vitro and in vivo evidence that Jagged-1/Notch signaling is activated in TGFβ2-stimulated EMT, and blockade of Notch signaling can reverse lens epithelial cells (LECs) EMT and lens fibrosis. Given the general involvement of EMT in most fibrotic diseases, cancer metastasis and recurrence, miR-26 family and Notch pathway may have therapeutic uses in treating fibrotic diseases and cancers.

scholarly journals Polarity and epithelial-mesenchymal transition of retinal pigment epithelial cells in proliferative vitreoretinopathy

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10136
Author(s):  
Hui Zou ◽  
Chenli Shan ◽  
Linlin Ma ◽  
Jia Liu ◽  
Ning Yang ◽  
...  
Keyword(s):  
Proliferative Vitreoretinopathy ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Retinal Pigment ◽  
Notch Pathway ◽  
Retinal Pigment Epithelial Cells ◽  
Cell Contact ◽  
Mesenchymal Transition ◽  
Rpe Cells ◽  
Cell Cell

Under physiological conditions, retinal pigment epithelium (RPE) is a cellular monolayer composed of mitotically quiescent cells. Tight junctions and adherens junctions maintain the polarity of RPE cells, and are required for cellular functions. In proliferative vitreoretinopathy (PVR), upon retinal tear, RPE cells lose cell-cell contact, undergo epithelial-mesenchymal transition (EMT), and ultimately transform into myofibroblasts, leading to the formation of fibrocellular membranes on both surfaces of the detached retina and on the posterior hyaloids, which causes tractional retinal detachment. In PVR, RPE cells are crucial contributors, and multiple signaling pathways, including the SMAD-dependent pathway, Rho pathway, MAPK pathways, Jagged/Notch pathway, and the Wnt/β-catenin pathway are activated. These pathways mediate the EMT of RPE cells, which play a key role in the pathogenesis of PVR. This review summarizes the current body of knowledge on the polarized phenotype of RPE, the role of cell-cell contact, and the molecular mechanisms underlying the RPE EMT in PVR, emphasizing key insights into potential approaches to prevent PVR.

scholarly journals A mechanism-based computational model to capture the interconnections among epithelial-mesenchymal transition, cancer stem cells and Notch-Jagged signaling

2018 ◽  
Author(s):  
Federico Bocci ◽  
Mohit K. Jolly ◽  
Jason George ◽  
Herbert Levine ◽  
José N. Onuchic
Keyword(s):  
Computational Model ◽  
Notch Signaling ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Cell Formation ◽  
Notch Pathway ◽  
Therapeutic Resistance ◽  
Heterogeneous Distribution ◽  
Mesenchymal Transition ◽  
Cancer Types

AbstractEpithelial-mesenchymal transition (EMT) and cancer stem cell formation (CSCs) are two fundamental and well-studied processes contributing to cancer metastasis and tumor relapse. Cells can undergo a partial EMT to attain a hybrid epithelial/mesenchymal (E/M) phenotype or a complete EMT to attain a mesenchymal one. Similarly, cells can reversibly gain or lose ‘stemness’. This plasticity in cell states is modulated by signaling pathways such as Notch. However, the interconnections among the cell states enabled by EMT, CSCs and Notch signaling remain elusive. Here, we devise a computational model to investigate the coupling among the core decision-making circuits for EMT, CSCs and the Notch pathway. Our model predicts that hybrid E/M cells are most likely to associate with stemness traits and exhibit enhanced Notch-Jagged signaling – a pathway that is implicated in therapeutic resistance. Further, we show that the position of the ‘stemness window’ on the ‘EMT axis’ is varied by altering the coupling strength between EMT and CSC circuits, and/or modulating Notch signaling. Finally, we analyze the gene expression profile of CSCs from several cancer types and observe a heterogeneous distribution along the ‘EMT axis’, suggesting that different subsets of CSCs may exist with varying phenotypes along the epithelial-mesenchymal plasticity axis. Our computational model offers insights into the complex EMT-stemness interplay and provides a platform to investigate the effects of therapeutic perturbations such as treatment with metformin, a common anti-diabetic drug that has been associated with decreased cancer incidence and increased lifespan of patients. Our mechanism-based model helps explain how metformin can both inhibit EMT and blunt the aggressive potential of CSCs simultaneously, by driving the cells out of a hybrid E/M stem-like state with enhanced Notch-Jagged signaling.

scholarly journals Breast tumor cells promotes the horizontal propagation of EMT, stemness, and metastasis by transferring the MAP17 protein between subsets of neoplastic cells

Oncogenesis ◽  
2020 ◽  
Vol 9 (10) ◽  
Author(s):  
José Manuel García-Heredia ◽  
Daniel Otero-Albiol ◽  
Marco Pérez ◽  
Elena Pérez-Castejón ◽  
Sandra Muñoz-Galván ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Tumor Cells ◽  
Epithelial Mesenchymal Transition ◽  
Notch Pathway ◽  
Metastatic Potential ◽  
Tumor Evolution ◽  
Neoplastic Cells ◽  
Mesenchymal Transition

Abstract MAP17 (PDZK1IP1) is a small protein regulating inflammation and tumor progression, upregulated in a broad range of carcinomas. MAP17 levels increase during tumor progression in a large percentage of advanced tumors. In the present work, we explored the role of this protein shaping tumor evolution. Here we show that in breast cancer, cells increased MAP17 levels in tumors by demethylation induced multiple changes in gene expression through specific miRNAs downregulation. These miRNA changes are dependent on Notch pathway activation. As a consequence, epithelial mesenchymal transition (EMT) and stemness are induced promoting the metastatic potential of these cells both in vitro and in vivo. Furthermore, MAP17 increased the exosomes in tumor cells, where MAP17 was released as cargo, and this horizontal propagation also increased the EMT in the recipient cells. Importantly, an antibody against MAP17 in the media reduces the EMT and stemness alterations promoted by the conditioned media from MAP17-expressing cells. Therefore, MAP17 expression promotes the horizontal propagation of EMT and metastasis by transferring the MAP17 protein between subsets of neoplastic cells. Thus, MAP17 can be used to describe a new mechanism for cell malignity at distance, without the involvement of genetic or epigenetic modifications. MAP17 can also be taken in consideration as new target for metastatic high-grade breast tumors.

Abstract B17: Sox9 mediates Notch pathway-induced epithelial-mesenchymal transition (EMT) in lung adenocarcinoma.

2014 ◽  
Vol 20 (2 Supplement) ◽  
pp. B17-B17
Author(s):  
Kathleen Capaccione ◽  
Xuehui Hong ◽  
Katherine M. Morgan ◽  
Wenyu Liu ◽  
Thaddeus Allen ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Notch Pathway ◽  
Mesenchymal Transition

Abstract 3309: Blocking the Notch pathway inhibits the epithelial-mesenchymal transition (EMT) status in lung cancer and alters chemoresistance

2012 ◽  
Author(s):  
Khaled A. Hassan ◽  
Luo Wang ◽  
Paige O'Dowd ◽  
Gwangil Kim ◽  
Hasan Korkaya ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Notch Pathway ◽  
Mesenchymal Transition

scholarly journals The Mouse Snail Gene Encodes a Key Regulator of the Epithelial-Mesenchymal Transition

2001 ◽  
Vol 21 (23) ◽  
pp. 8184-8188 ◽  
Author(s):  
Ethan A. Carver ◽  
Rulang Jiang ◽  
Yu Lan ◽  
Kathleen F. Oram ◽  
Thomas Gridley
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Mouse Embryos ◽  
Marker Genes ◽  
Germ Layer ◽  
Apical Surface ◽  
Transcriptional Repressors ◽  
Mesenchymal Transition ◽  
Snail Family ◽  
Snail Gene ◽  
E Cadherin

ABSTRACT Snail family genes encode DNA binding zinc finger proteins that act as transcriptional repressors. Mouse embryos deficient for the Snail (Sna) gene exhibit defects in the formation of the mesoderm germ layer. In Sna −/− mutant embryos, a mesoderm layer forms and mesodermal marker genes are induced but the mutant mesoderm is morphologically abnormal. Lacunae form within the mesoderm layer of the mutant embryos, and cells lining these lacunae retain epithelial characteristics. These cells resemble a columnar epithelium and have apical-basal polarity, with microvilli along the apical surface and intercellular electron-dense adhesive junctions that resemble adherens junctions. E-cadherin expression is retained in the mesoderm of the Sna −/− embryos. These defects are strikingly similar to the gastrulation defects observed insnail-deficient Drosophila embryos, suggesting that the mechanism of repression of E-cadherin transcription by Snail family proteins may have been present in the metazoan ancestor of the arthropod and mammalian lineages.

scholarly journals ZEB1-activated LINC01123 accelerates the malignancy in lung adenocarcinoma through NOTCH signaling pathway

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Miao Zhang ◽  
Yaguang Han ◽  
Yi Zheng ◽  
Yan Zhang ◽  
Xin Zhao ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Transcriptional Activation ◽  
Epithelial Mesenchymal Transition ◽  
Notch Pathway ◽  
Notch Signaling Pathway ◽  
Mesenchymal Transition ◽  
Functional Changes ◽  
Signaling Activation

AbstractGrowing incidence of lung adenocarcinoma (LUAD) has been detected recently. Multiple long non-coding RNAs (lncRNAs) have been proven as tumor facilitators or inhibitors by extensive works. Present study concentrated on characterizing the potential role of LINC01123 in LUAD. We explored the differential expression of LINC01123 through qRT-PCR and found the amplification of LINC01123 in LUAD cell lines. It was ascertained that LINC01123 was definitely responsible for the malignant processes of LUAD cells. Further, we validated the ceRNA network of LINC01123/miR-449b-5p/NOTCH1 in LUAD via mechanical experiments. As a transcriptional factor related to epithelial mesenchymal transition (EMT), ZEB1 was responsible for the transcriptional activation of both LINC01123 and NOTCH1. The involvement of NOTCH signaling in LUAD was interrogated through evaluating functional changes after treating with FLI-06 (NOTCH pathway suppressor). It showed that FLI-06-caused NOTCH signaling inactivation suppressed malignant functions in LUAD cells. Additionally, LINC01123 facilitated NOTCH1-dependent NOTCH signaling activation. Rescue experiments probed the modulatory function of LINC01123/miR-449b-5p/NOTCH1 in LUAD cellular processes. Altogether, ZEB1-activated LINC01123 accelerates the malignancy in LUAD through miR-449b-5p/NOTCH1 axis-mediated NOTCH signaling pathway, while NOTCH1 boosts ZEB1 in return. These observations suggest the huge potential of LINC01123 as a new target for LUAD therapy.

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