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Article
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Cell diversity and plasticity during atrioventricular heart valve EMTs
Lotto et al. delineate cell diversity and mechanisms during heart valve development using scRNA-seq. They identify distinct cell types and states, the emergence of epithelial-mesenchymal plasticity, and cell interactions that may govern this process.
- Jeremy Lotto
- , Rebecca Cullum
- & Pamela A. Hoodless
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Article
| Open Access
YBX1 integration of oncogenic PI3K/mTOR signalling regulates the fitness of malignant epithelial cells
The understanding of molecular mechanisms in different subtypes of head and neck cancer (HNC) will define subtype-specific treatment options. Here the authors show that PI3K-phospho-YBX1 axis promotes tumour growth in basal subtype of HNC, while unphosphorylated YBX1 acts as a suppressor of metastasis in the mesenchymal subtype with inactive PI3K signalling.
- Yuchen Bai
- , Carolin Gotz
- & Charbel Darido
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Article
| Open Access
Genomic and microenvironmental heterogeneity shaping epithelial-to-mesenchymal trajectories in cancer
The intermediate states of the epithelial-to-mesenchymal transition (EMT) in cancer require further molecular characterisation. Here, the authors develop a method to evaluate EMT transformation and trajectories in cancer transcriptomics data, characterising EMT macro-states, including a hybrid state, and EMT hallmarks.
- Guidantonio Malagoli Tagliazucchi
- , Anna J. Wiecek
- & Maria Secrier
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Article
| Open Access
Parallelized multidimensional analytic framework applied to mammary epithelial cells uncovers regulatory principles in EMT
Epithelial-to-mesenchymal transition (EMT) is a complex process regulated at multiple molecular levels. Here, the authors implement an analytic framework - PAMAF - to integrate data from twelve distinct omics modalities, which they use to understand the molecular changes and regulation during EMT in vitro.
- Indranil Paul
- , Dante Bolzan
- & Andrew Emili
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Article
| Open Access
FOXQ1 recruits the MLL complex to activate transcription of EMT and promote breast cancer metastasis
Forkhead box transcription factor, FOXQ1 is reported to promote epithelial-mesenchymal transition (EMT) and cancer metastasis. Here the authors show that FOXQ1 recruits the KMT2/MLL histone methyltransferase complex as a transcriptional coactivator to activate EMT programme in breast cancer.
- Allison V. Mitchell
- , Ling Wu
- & Guojun Wu
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Article
| Open Access
The TFEB-TGIF1 axis regulates EMT in mouse epicardial cells
Epithelial-mesenchymal transition (EMT) is a complex process involved in organogenesis. Here, the authors show that the transcription factor EB (TFEB) regulates EMT in epicardium during heart development by tuning sensitivity to TGFβ signaling.
- Elena Astanina
- , Gabriella Doronzo
- & Federico Bussolino
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Article
| Open Access
Purine nucleotide depletion prompts cell migration by stimulating the serine synthesis pathway
Nucleotides are essential for different biological processes and have been also associated to cancer development. Depleting cellular nucleotides is a strategy commonly employed to target cancers. Here, the authors show that purine depletion induces serine synthesis to promote cancer cell migration and metastasis.
- Mona Hoseini Soflaee
- , Rushendhiran Kesavan
- & Gerta Hoxhaj
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Article
| Open Access
Coordination of endothelial cell positioning and fate specification by the epicardium
It remains unclear how spatial information controls endothelial cell identity and behavior in the developing heart. Here the authors perform single cell RNA sequencing at key developmental timepoints in mice to interrogate cellular contributions to coronary vessel patterning and maturation in the epicardium.
- Pearl Quijada
- , Michael A. Trembley
- & Eric M. Small
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Article
| Open Access
β-Pix-dependent cellular protrusions propel collective mesoderm migration in the mouse embryo
Mesodermal directional cell migration is needed to establish body plan but how this is regulated is unclear. Here, the authors show that loss of the guanine nucleotide exchange factor for Rac1 and Cdc42, β-Pix, at mouse gastrulation disrupts the orderly, collective anterior migration of mesoderm cells due to defective cell protrusions.
- Tatiana Omelchenko
- , Alan Hall
- & Kathryn V. Anderson
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Article
| Open Access
In primary airway epithelial cells, the unjamming transition is distinct from the epithelial-to-mesenchymal transition
During repair, development, or cancer metastasis, epithelial cells can become migratory through partial or full epithelial to mesenchymal transition (EMT). Here, the authors report that differentiated epithelial collectives may undergo cooperative and collective migration without evidence of partial EMT through an unjamming transition (UJT).
- Jennifer A. Mitchel
- , Amit Das
- & Jin-Ah Park
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Article
| Open Access
A self-sustaining endocytic-based loop promotes breast cancer plasticity leading to aggressiveness and pro-metastatic behavior
It is unclear if genetic alterations in endocytic proteins play a causal role in high incidence human cancers. Here, the authors report the oncogenic role of Epsin3 (EPN3) in breast cancer, and show EPN3 to drive tumorigenesis through induction of a partial epithelial mesenchymal transition state and a TGFβ-dependent regulatory loop that promotes cellular plasticity and invasive behaviour.
- Irene Schiano Lomoriello
- , Giovanni Giangreco
- & Pier Paolo Di Fiore
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Article
| Open Access
ZEB1/NuRD complex suppresses TBC1D2b to stimulate E-cadherin internalization and promote metastasis in lung cancer
Non-small cell lung cancer (NSCLC) is often associated with metastasis to the lungs. Here, the authors perform independent screens and identify NuRD as a co-repressor of ZEB1, and demonstrate TBC1D2b as a downstream target of ZEB1/NuRD complex regulating NSCLC metastasis.
- Roxsan Manshouri
- , Etienne Coyaud
- & Don L. Gibbons
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| Open Access
Mechanical impact of epithelial−mesenchymal transition on epithelial morphogenesis in Drosophila
Tissue folding is a critical process during developmental morphogenesis. Here, Gracia et al. use live imaging, laser ablation and in silico modelling to demonstrate that cells entering EMT generate orthogonal forces necessary to drive mesoderm invagination in Drosophila.
- Mélanie Gracia
- , Sophie Theis
- & Magali Suzanne
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| Open Access
Switch-like enhancement of epithelial-mesenchymal transition by YAP through feedback regulation of WT1 and Rho-family GTPases
Reorganisation of the extracellular matrix (ECM) controls processes involving epithelial-mesenchymal transition (EMT). Here, the authors show that EMT occurring in epithelial cells on a fabricated nano-engineered cell adhesion surface is triggered by mechanical cues from the ECM.
- JinSeok Park
- , Deok-Ho Kim
- & Andre Levchenko
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Article
| Open Access
Genetic dissection of the miR-200–Zeb1 axis reveals its importance in tumor differentiation and invasion
In vivo studies on the regulation of the epithelial-mesenchymal transition (EMT) within a physiological context are lacking. Here it is shown that miR-200 ablation in the Rip-Tag2 insulinoma mouse model induces beta-cell dedifferentiation, EMT and tumor invasion, and that disruption of Zeb1 regulation by miR-200c is sufficient to drive EMT.
- Alexandra C. Title
- , Sue-Jean Hong
- & Markus Stoffel
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Article
| Open Access
miR-1199-5p and Zeb1 function in a double-negative feedback loop potentially coordinating EMT and tumour metastasis
miRNAs have been involved in tumour development and progression. Here the authors uncover a double feedback loop between miR-1199-5p and the Zeb1, potentially coordinating a protein involved in epithelial mesenchymal transition and tumour metastasis.
- Maren Diepenbruck
- , Stefanie Tiede
- & Gerhard Christofori
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Article
| Open Access
An apicobasal gradient of Rac activity determines protrusion form and position
Polarized epithelial cells must correctly position a wide range of subcellular structures. Here the authors demonstrate an apicobasal gradient of Rac GTPase activity, which is maintained by polarity proteins inDrosophilaepithelial sheets, and is required to maintain actin-dependent protrusion form and position.
- Africa Couto
- , Natalie Ann Mack
- & Marios Georgiou
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| Open Access
A cell-based computational model of early embryogenesis coupling mechanical behaviour and gene regulation
Embryonic development is a complex process where genetic and biochemical information direct morphogenesis. Here the authors describe MecaGen, an agent-based model and simulation platform of multicellular development designed to allow a quantitative comparison between simulations and real biological data.
- Julien Delile
- , Matthieu Herrmann
- & René Doursat
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| Open Access
αE-catenin inhibits YAP/TAZ activity to regulate signalling centre formation during tooth development
It is unclear which signals regulate the establishment of the tooth signalling centre, the enamel knot (EK). Here, the authors show that EK formation depends on αE-catenin, which acts to restrict the Hippo pathway transcription factors Yes-associated protein (YAP) and TAZ.
- Chun-Ying Li
- , Jimmy Hu
- & Ophir D. Klein
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Article
| Open Access
The histone variant H2A.X is a regulator of the epithelial–mesenchymal transition
The histone H2A variants are involved in DNA repair, gene regulation and cancer development. In this study, the authors unravel an additional role for H2A.X in the regulation of mesenchymal-like traits and activation of the EMT transcription factors, Slug and ZEB1, in colon cancer cells.
- Urbain Weyemi
- , Christophe E. Redon
- & William M. Bonner
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NACA deficiency reveals the crucial role of somite-derived stromal cells in haematopoietic niche formation
How do stromal cells contribute to the haematopoietic stem cell (HSC) niche? In zebrafish, Murayama et al. identify somite-derived stromal cells in the first niche where HSCs home, and depletion of the nascent polypeptide-associated complex alpha subunit in these cells prevents HSC maturation.
- Emi Murayama
- , Milka Sarris
- & Philippe Herbomel
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Article
| Open Access
Loss of ATM accelerates pancreatic cancer formation and epithelial–mesenchymal transition
Mutations in the serine/threonine kinase ataxia teleangiectasia mutated (ATM) have been linked to pancreatic ductal adenocarcinoma (PDAC) cohorts. Here Russellet al. show that loss of ATM induces a greater number of proliferative precursor lesions in a mouse model, recapitulating many features of human PDAC subtypes.
- Ronan Russell
- , Lukas Perkhofer
- & Alexander Kleger
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Article
| Open Access
DOT1L cooperates with the c-Myc-p300 complex to epigenetically derepress CDH1 transcription factors in breast cancer progression
DOT1L is an anti-cancer therapeutic target in leukaemia but has a poorly understood role in solid tumours. Here the authors show that DOT1L expression is associated with poor survival and aggressive cancers by helping to epigenetically activate the epithelial-mesenchymal transition during breast cancer progression.
- Min-Hyung Cho
- , Ji-Hye Park
- & Gu Kong
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PYK2 sustains endosomal-derived receptor signalling and enhances epithelial-to-mesenchymal transition
Proline-rich tyrosine kinase 2 (PYK2) has been previously involved in the positive regulation of epithelial-to-mesenchymal transition (EMT); however, the mechanisms were not known. Here the authors uncover key roles of PYK2 during EGF-induced EMT in human mammary cell lines involving STAT3 and c-MET.
- Nandini Verma
- , Omer Keinan
- & Sima Lev
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Article
| Open Access
Gd-metallofullerenol nanomaterial as non-toxic breast cancer stem cell-specific inhibitor
A metallofullerenol nanomaterial, Gd@C82(OH)22, was shown to inhibit growth of several solid cancers in preclinical models and yet exhibit low toxicity. Herein the authors show that Gd@C82(OH)22functions as an inhibitor of breast cancer stem cell function via blocking TGF-β and HIF-1α signalling, while sparing normal tissue.
- Ying Liu
- , Chunying Chen
- & Yuliang Zhao
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Article
| Open Access
Concomitant Notch activation and p53 deletion trigger epithelial-to-mesenchymal transition and metastasis in mouse gut
Metastasizing tumour cells undergo epithelial-to-mesenchymal transition. Using both bioinformatic and in vivo approaches, Chanrion et al.identify combined Notch activation and p53 inactivation as a potent inducer of this transition, and apply this to create a highly metastatic tumour model in mice.
- Maia Chanrion
- , Inna Kuperstein
- & Sylvie Robine
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Helicobacter pylori CagA promotes Snail-mediated epithelial–mesenchymal transition by reducing GSK-3 activity
Gastric cancer is associated with H. pylori infection and these tumours frequently show features of epithelial–mesenchymal transition (EMT). Here, the authors show that the H. pylorivirulence protein, CagA, reduces the activity of GSK3b, which leads to the stabilization of Snail, a protein that induces EMT.
- Da-Gyum Lee
- , Hyun Sil Kim
- & Yong Chan Lee
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Article
| Open Access
microRNA-181a has a critical role in ovarian cancer progression through the regulation of the epithelial–mesenchymal transition
Ovarian cancer is often diagnosed at a late stage when metastasis has already occurred. In this study, Parikh et al.show that mir-181a is involved in mediating the epithelial-to-mesenchymal transition in ovarian cancer, leading to activation of the TGF-β signalling pathway and metastasis.
- Aditya Parikh
- , Christine Lee
- & Analisa DiFeo
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MicroRNA-30c inhibits human breast tumour chemotherapy resistance by regulating TWF1 and IL-11
The role of microRNAs in chemotherapy resistance remains to be elucidated. Bockhorn et al.report that microRNA-30c, a human breast tumour prognostic marker, has a key role by targeting the epithelial-to-mesenchymal transition promoter twinfilin 1 and downstream interleukin-11 expression.
- Jessica Bockhorn
- , Rachel Dalton
- & Huiping Liu
A circular RNA activated by TGFβ promotes tumor metastasis through enhancing IGF2BP3-mediated PDPN mRNA stability