scholarly journals Epigenetic inactivation of miR-203 as a key step in neural crest epithelial-to-mesenchymal transition

2018 ◽  
Author(s):  
Estefanía Sánchez-Vásquez ◽  
Marianne E. Bronner ◽  
Pablo H. Strobl-Mazzulla
Keyword(s):  
Neural Crest ◽  
Dna Methyltransferase ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
De Novo ◽  
Mirna Gene ◽  
Mesenchymal Transition ◽  
Regulatory Circuit ◽  
Epigenetic Repression ◽  
Neural Crest Migration

AbstractmiR-203 is a tumor-suppressor microRNA with known functions in cancer metastasis. Here, we explore its normal developmental role in the context of neural crest development. As neural crest cells undergo an epithelial-to-mesenchymal transition to emigrate from the neural tube, miR-203 displays a reciprocal expression pattern with key regulators of neural crest delamination, Phf12 and Snail2, and interacts with their 3’UTRs. Ectopic maintenance of miR-203 inhibits neural crest migration, whereas its functional inhibition using a “sponge” vector promotes premature neural crest delamination. Bisulfite sequencing further shows that epigenetic repression of miR-203 is mediated by the de novo DNA methyltransferase DNMT3B, whose recruitment to regulatory regions on the miR-203 locus is directed by SNAIL2 in a negative feedback loop. These findings reveal an important role for miR-203 in an epigenetic-microRNA regulatory network that influences the timing of neural crest delamination.Summary statementThe EMT is a highly conserved process, involving similar levels of regulation in both neural crest and cancer cells. Our work shows an epigenetic-miRNA-gene regulatory circuit, conserved in cancer, which controls the timing of neural crest EMT as well.

scholarly journals The hypoxia factor Hif-1α controls neural crest chemotaxis and epithelial to mesenchymal transition

2013 ◽  
Vol 201 (5) ◽  
pp. 759-776 ◽  
Author(s):  
Elias H. Barriga ◽  
Patrick H. Maxwell ◽  
Ariel E. Reyes ◽  
Roberto Mayor
Keyword(s):  
Neural Crest ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Neural Crest Cells ◽  
Embryonic Cell ◽  
Zebrafish Embryos ◽  
Mesenchymal Transition ◽  
Metastasis Inhibition ◽  
Neural Crest Migration ◽  
Transcription Factor 1

One of the most important mechanisms that promotes metastasis is the stabilization of Hif-1 (hypoxia-inducible transcription factor 1). We decided to test whether Hif-1α also was required for early embryonic development. We focused our attention on the development of the neural crest, a highly migratory embryonic cell population whose behavior has been likened to cancer metastasis. Inhibition of Hif-1α by antisense morpholinos in Xenopus laevis or zebrafish embryos led to complete inhibition of neural crest migration. We show that Hif-1α controls the expression of Twist, which in turn represses E-cadherin during epithelial to mesenchymal transition (EMT) of neural crest cells. Thus, Hif-1α allows cells to initiate migration by promoting the release of cell–cell adhesions. Additionally, Hif-1α controls chemotaxis toward the chemokine SDF-1 by regulating expression of its receptor Cxcr4. Our results point to Hif-1α as a novel and key regulator that integrates EMT and chemotaxis during migration of neural crest cells.

Mechanisms of Neural Crest Migration

2018 ◽  
Vol 52 (1) ◽  
pp. 43-63 ◽  
Author(s):  
András Szabó ◽  
Roberto Mayor
Keyword(s):  
Neural Crest ◽  
Cell Population ◽  
Epithelial To Mesenchymal Transition ◽  
Neural Crest Cells ◽  
Cell Types ◽  
Embryonic Cell ◽  
Mesenchymal Transition ◽  
Chain Migration ◽  
Mass Migration ◽  
Neural Crest Migration

Neural crest cells are a transient embryonic cell population that migrate collectively to various locations throughout the embryo to contribute a number of cell types to several organs. After induction, the neural crest delaminates and undergoes an epithelial-to-mesenchymal transition before migrating through intricate yet characteristic paths. The neural crest exhibits a variety of migratory behaviors ranging from sheet-like mass migration in the cephalic regions to chain migration in the trunk. During their journey, neural crest cells rely on a range of signals both from their environment and within the migrating population for navigating through the embryo as a collective. Here we review these interactions and mechanisms, including chemotactic cues of neural crest cells’ migration.

scholarly journals Early Development of The Trunk Neural Crest Cells in the Egyptian Cobra Naja H. Haje

2021 ◽  
Author(s):  
Eraqi R. Khannoon ◽  
Christian Alvarado ◽  
Maria Elena Elena de Bellard
Keyword(s):  
Embryonic Development ◽  
Neural Crest ◽  
Early Development ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Early Stage ◽  
Neural Crest Cells ◽  
Migratory Behavior ◽  
Mesenchymal Transition ◽  
Trunk Neural Crest

Abstract Background: Trunk neural crest cells (TNCC) are representing a model for epithelial to mesenchymal transition, this correlates the importance of studying the migration of these cells to cancer metastasis. Reptiles are unique group of animals being very morphologically diverse and their close position to synapsid leading to mammals. Recently, more publications focused on the migratory behavior of trunk NCC during embryonic development of squamates. Only one colubrid snake has been studied so far regarding the NCC migration. Results: Here we follow the migratory behavior of TNCC with HNK1 in the elapid snake Naja h. haje from early stage to 14 days postoviposition. Comparing the colubrid snake with the Egyptian cobra showed that both snakes overall follow the same TNCC migratory pathways of both birds and mammals by following the rostral and avoiding the caudal portions of the somites. Conclusions: First, TNCC intra-somitic migration as observed in turtles supports a contributing role for TNCC to scale precursors. Second, our observation of significant numbers of migrating TNCC in the intersomitic pathway suggest interesting evolutionary differences. Together, our present results of the Egyptian cobra in combination with those on a colubrid and turtle supports intersomitic TNCC as a unique reptile phenomena.

Conservation of Epithelial-to-Mesenchymal Transition Process in Neural Crest Cells and Metastatic Cancer

2021 ◽  
pp. 1-22
Author(s):  
April Zhang ◽  
Hira Aslam ◽  
Neha Sharma ◽  
Aryeh Warmflash ◽  
Walid D. Fakhouri
Keyword(s):  
Neural Crest ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Intracellular Signaling ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Metastatic Cancer ◽  
Neural Crest Cell ◽  
Cancer Type ◽  
Mesenchymal Transition

Epithelial to mesenchymal transition (EMT) is a highly conserved cellular process in several species, from worms to humans. EMT plays a fundamental role in early embryogenesis, wound healing, and cancer metastasis. For neural crest cell (NCC) development, EMT typically results in forming a migratory and potent cell population that generates a wide variety of cell and tissue, including cartilage, bone, connective tissue, endocrine cells, neurons, and glia amongst many others. The degree of conservation between the signaling pathways that regulate EMT during development and metastatic cancer (MC) has not been fully established, despite ample studies. This systematic review and meta-analysis dissects the major signaling pathways involved in EMT of NCC development and MC to unravel the similarities and differences. While the FGF, TGFβ/BMP, SHH, and NOTCH pathways have been rigorously investigated in both systems, the EGF, IGF, HIPPO, Factor Receptor Superfamily, and their intracellular signaling cascades need to be the focus of future NCC studies. In general, meta-analyses of the associated signaling pathways show a significant number of overlapping genes (particularly ligands, transcription regulators, and targeted cadherins) involved in each signaling pathway of both systems without stratification by body segments and cancer type. Lack of stratification makes it difficult to meaningfully evaluate the intracellular downstream effectors of each signaling pathway. Finally, pediatric neuroblastoma and melanoma are NCC-derived malignancies, which emphasize the importance of uncovering the EMT events that convert NCC into treatment-resistant malignant cells.

scholarly journals Ovalitenone Inhibits the Migration of Lung Cancer Cells via the Suppression of AKT/mTOR and Epithelial-to-Mesenchymal Transition

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 638
Author(s):  
Kittipong Sanookpan ◽  
Nongyao Nonpanya ◽  
Boonchoo Sritularak ◽  
Pithi Chanvorachote
Keyword(s):  
Lung Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Colony Formation ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Cancer metastasis is the major cause of about 90% of cancer deaths. As epithelial-to-mesenchymal transition (EMT) is known for potentiating metastasis, this study aimed to elucidate the effect of ovalitenone on the suppression of EMT and metastasis-related behaviors, including cell movement and growth under detached conditions, and cancer stem cells (CSCs), of lung cancer cells. Methods: Cell viability and cell proliferation were determined by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazo-liumbromide (MTT) and colony formation assays. Cell migration and invasion were analyzed using a wound-healing assay and Boyden chamber assay, respectively. Anchorage-independent cell growth was determined. Cell protrusions (filopodia) were detected by phalloidin-rhodamine staining. Cancer stem cell phenotypes were assessed by spheroid formation. The proteins involved in cell migration and EMT were evaluated by Western blot analysis and immunofluorescence staining. Results: Ovalitenone was used at concentrations of 0–200 μM. While it caused no cytotoxic effects on lung cancer H460 and A549 cells, ovalitenone significantly suppressed anchorage-independent growth, CSC-like phenotypes, colony formation, and the ability of the cancer to migrate and invade cells. The anti-migration activity was confirmed by the reduction of filopodia in the cells treated with ovalitenone. Interestingly, we found that ovalitenone could significantly decrease the levels of N-cadherin, snail, and slug, while it increased E-cadherin, indicating EMT suppression. Additionally, the regulatory signaling of focal adhesion kinase (FAK), ATP-dependent tyrosine kinase (AKT), the mammalian target of rapamycin (mTOR), and cell division cycle 42 (Cdc42) was suppressed by ovalitenone. Conclusions: The results suggest that ovalitenone suppresses EMT via suppression of the AKT/mTOR signaling pathway. In addition, ovalitenone exhibited potential for the suppression of CSC phenotypes. These data reveal the anti-metastasis potential of the compound and support the development of ovalitenone treatment for lung cancer therapy.

scholarly journals Cadherin-6B proteolysis promotes the neural crest cell epithelial-to-mesenchymal transition through transcriptional regulation

2016 ◽  
Vol 215 (5) ◽  
pp. 735-747 ◽  
Author(s):  
Andrew T. Schiffmacher ◽  
Vivien Xie ◽  
Lisa A. Taneyhill
Keyword(s):  
Neural Crest ◽  
Epithelial To Mesenchymal Transition ◽  
Neural Crest Cell ◽  
Cranial Neural Crest ◽  
Mesenchymal Transition ◽  
Effector Genes ◽  
A Disintegrin And Metalloproteinase ◽  
And Migration ◽  
Cranial Neural Crest Cells

During epithelial-to-mesenchymal transitions (EMTs), cells disassemble cadherin-based junctions to segregate from the epithelia. Chick premigratory cranial neural crest cells reduce Cadherin-6B (Cad6B) levels through several mechanisms, including proteolysis, to permit their EMT and migration. Serial processing of Cad6B by a disintegrin and metalloproteinase (ADAM) proteins and γ-secretase generates intracellular C-terminal fragments (CTF2s) that could acquire additional functions. Here we report that Cad6B CTF2 possesses a novel pro-EMT role by up-regulating EMT effector genes in vivo. After proteolysis, CTF2 remains associated with β-catenin, which stabilizes and redistributes both proteins to the cytosol and nucleus, leading to up-regulation of β-catenin, CyclinD1, Snail2, and Snail2 promoter-based GFP expression in vivo. A CTF2 β-catenin–binding mutant, however, fails to alter gene expression, indicating that CTF2 modulates β-catenin–responsive EMT effector genes. Notably, CTF2 association with the endogenous Snail2 promoter in the neural crest is β-catenin dependent. Collectively, our data reveal how Cad6B proteolysis orchestrates multiple pro-EMT regulatory inputs, including CTF2-mediated up-regulation of the Cad6B repressor Snail2, to ensure proper cranial neural crest EMT.

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