scholarly journals Riding the crest of the wave: parallels between the neural crest and cancer in epithelial-to-mesenchymal transition and migration

2013 ◽  
Vol 5 (4) ◽  
pp. 511-522 ◽  
Author(s):  
Davalyn R. Powell ◽  
Alex J. Blasky ◽  
Steven G. Britt ◽  
Kristin B. Artinger
Keyword(s):  
Neural Crest ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
And Migration

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.

scholarly journals Cadherin-11 is required for neural crest determination and survival

2020 ◽  
Author(s):  
Subrajaa Manohar ◽  
Alberto Camacho ◽  
Crystal D. Rogers
Keyword(s):  
Cell Migration ◽  
Neural Crest ◽  
Neural Tube ◽  
Epithelial To Mesenchymal Transition ◽  
Congenital Defects ◽  
Embryonic Cells ◽  
Developmental Defects ◽  
Mesenchymal Transition ◽  
Dorsal Neural Tube ◽  
And Migration

AbstractNeural crest (NC) cells are multipotent embryonic cells that form melanocytes, craniofacial bone and cartilage, and the peripheral nervous system in vertebrates. NC cells express many cadherin proteins, which control their specification, epithelial to mesenchymal transition (EMT), migration, and mesenchymal to epithelial transition. Abnormal NC development leads to congenital defects including craniofacial clefts as well as NC-derived cancers. Here, we identify the role of the type II cadherin protein, Cadherin-11 (CDH11), in early chicken NC development. CDH11 is crucial for NC cell migration in amphibian embryos and is linked to cell survival, proliferation, and migration in cancer cells. It has been linked to the complex neurocristopathy disorder, Elsahy‐Waters Syndrome, in humans. Using immunohistochemistry (IHC), we determined that CDH11 protein has dynamic expression that is first co-localized with neural progenitors in early embryos and subsequently upregulated specifically in NC cells as they are specified in the dorsal neural tube prior to migration. We identified that loss of CDH11 led to a reduction of bonafide NC cells in the dorsal neural tube combined with defects in cell migration and survival. Loss of CDH11 increased p53-mediated programmed-cell death, and blocking the p53 pathway rescued the NC phenotype. Our findings demonstrate an early requirement for CDH11 in NC development, and may increase our understanding of early cadherin-related NC developmental defects.SummaryChicken Cadherin-11 (CDH11), which is expressed in neural crest (NC) cells prior to NC cell migration, is necessary for the determination and survival of the premigratory NC population.

scholarly journals From Neural Crest to Definitive Roof Plate: The Dynamic Behavior of the Dorsal Neural Tube

2021 ◽  
Vol 22 (8) ◽  
pp. 3911
Author(s):  
Dina Rekler ◽  
Chaya Kalcheim
Keyword(s):  
Neural Crest ◽  
Neural Tube ◽  
Epithelial To Mesenchymal Transition ◽  
Cell Types ◽  
Mesenchymal Transition ◽  
Dorsal Neural Tube ◽  
Roof Plate ◽  
Organizing Center ◽  
The Central Nervous System ◽  
And Migration

Research on the development of the dorsal neural tube is particularly challenging. In this highly dynamic domain, a temporal transition occurs between early neural crest progenitors that undergo an epithelial-to-mesenchymal transition and exit the neural primordium, and the subsequent roof plate, a resident epithelial group of cells that constitutes the dorsal midline of the central nervous system. Among other functions, the roof plate behaves as an organizing center for the generation of dorsal interneurons. Despite extensive knowledge of the formation, emigration and migration of neural crest progenitors, little is known about the mechanisms leading to the end of neural crest production and the transition into a roof plate stage. Are these two mutually dependent or autonomously regulated processes? Is the generation of roof plate and dorsal interneurons induced by neural tube-derived factors throughout both crest and roof plate stages, respectively, or are there differences in signaling properties and responsiveness as a function of time? In this review, we discuss distinctive characteristics of each population and possible mechanisms leading to the shift between the above cell types.

scholarly journals Draxin acts as a molecular rheostat of canonical Wnt signaling to control cranial neural crest EMT

2018 ◽  
Vol 217 (10) ◽  
pp. 3683-3697 ◽  
Author(s):  
Erica J. Hutchins ◽  
Marianne E. Bronner
Keyword(s):  
Wnt Signaling ◽  
Neural Crest ◽  
Neural Tube ◽  
Epithelial To Mesenchymal Transition ◽  
Cranial Neural Crest ◽  
Canonical Wnt Signaling ◽  
Mesenchymal Transition ◽  
Molecular Rheostat ◽  
Timing Of Initiation ◽  
Canonical Wnt

Neural crest cells undergo a spatiotemporally regulated epithelial-to-mesenchymal transition (EMT) that proceeds head to tailward to exit from the neural tube. In this study, we show that the secreted molecule Draxin is expressed in a transient rostrocaudal wave that mirrors this emigration pattern, initiating after neural crest specification and being down-regulated just before delamination. Functional experiments reveal that Draxin regulates the timing of cranial neural crest EMT by transiently inhibiting canonical Wnt signaling. Ectopic maintenance of Draxin in the cranial neural tube blocks full EMT; while cells delaminate, they fail to become mesenchymal and migratory. Loss of Draxin results in premature delamination but also in failure to mesenchymalize. These results suggest that a pulse of intermediate Wnt signaling triggers EMT and is necessary for its completion. Taken together, these data show that transient secreted Draxin mediates proper levels of canonical Wnt signaling required to regulate the precise timing of initiation and completion of cranial neural crest EMT.

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 Induction of the Epithelial-to-Mesenchymal Transition of Human Colorectal Cancer by Human TNF-β (Lymphotoxin) and its Reversal by Resveratrol

Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 704 ◽  
Author(s):  
Constanze Buhrmann ◽  
Mina Yazdi ◽  
Bastian Popper ◽  
Ajaikumar Kunnumakkara ◽  
Bharat Aggarwal ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Invasion Mechanism ◽  
Tnf Α ◽  
Anti Cancer ◽  
Targeted Agent ◽  
And Migration ◽  
Proliferation And Invasion ◽  
Necrosis Factor

Objective: Tumor necrosis factor-beta (TNF-β), as an inflammatory mediator that has been shown to promote tumorigenesis, induces NF-κB. Natural multi-targeted agent resveratrol in turn shows anti-inflammatory and anti-cancer properties. Epithelial-to-mesenchymal transition (EMT) allows cancer cells to turn into a motile state with invasive capacities and is associated with metastasis and development of cancer stem cells (CSC). However, TNF-β-induced EMT and the anti-invasion mechanism of resveratrol on CRC are not yet completely understood. Methods: We investigated the underlying molecular mechanisms of resveratrol on TNF-β/TNF-βR-induced EMT and migration of CRC cells (HCT116, RKO, SW480) in monolayer or 3D alginate cultures. Results: TNF-β, similar to TNF-α, induced significant cell proliferation, morphological change, from an epithelial to a spindle-like mesenchymal shape with the formation of filopodia and lamellipodia associated with the expression of EMT parameters (elevated vimentin and slug, reduced E-cadherin), increased migration/invasion, and formation of CSC in all CRC cells. Interestingly, these effects were dramatically decreased in the presence of resveratrol or anti-TNF-βR with TNF-β co-treatment, inducing biochemical changes to the mesenchymal-epithelial transition (MET), with a planar cell surface and suppressed formation of CSC cells. This was associated with a significant increase in apoptosis. Furthermore, we found that resveratrol suppressed TNF-β-induced NF-κB and NF-κB-regulated gene biomarkers associated with growth, proliferation, and invasion. Finally, TNF-βR interacts directly with focal adhesion kinase (FAK) and NF-κB. Conclusion: These results suggest that resveratrol down-regulates TNF-β/TNF-βR-induced EMT, at least in part via specific suppression of NF-κΒ and FAK in CRC cells.

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