Context specificity of the EMT transcriptional response

Cook, David P.; Vanderhyden, Barbara C.

doi:10.1038/s41467-020-16066-2

Cited by 193 publications

(341 citation statements)

References 62 publications

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“…Of note, cellular plasticity conferred by EMT and other mechanisms that lead to morphological and functional changes requires robust reprogramming of gene expression programs. For example, several thousand genes change their expression in a context-dependent manner during EMT [ 41 ]. These profound changes require multiple layers of regulation, from transcription, to post-transcriptional RNA processing, to translational and post-translational modifications.…”

Section: Introductionmentioning

confidence: 99%

RNA-Binding Proteins as Regulators of Migration, Invasion and Metastasis in Oral Squamous Cell Carcinoma

Weiße

Rosemann

Krauspe

et al. 2020

IJMS

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Nearly 7.5% of all human protein-coding genes have been assigned to the class of RNA-binding proteins (RBPs), and over the past decade, RBPs have been increasingly recognized as important regulators of molecular and cellular homeostasis. RBPs regulate the post-transcriptional processing of their target RNAs, i.e., alternative splicing, polyadenylation, stability and turnover, localization, or translation as well as editing and chemical modification, thereby tuning gene expression programs of diverse cellular processes such as cell survival and malignant spread. Importantly, metastases are the major cause of cancer-associated deaths in general, and particularly in oral cancers, which account for 2% of the global cancer mortality. However, the roles and architecture of RBPs and RBP-controlled expression networks during the diverse steps of the metastatic cascade are only incompletely understood. In this review, we will offer a brief overview about RBPs and their general contribution to post-transcriptional regulation of gene expression. Subsequently, we will highlight selected examples of RBPs that have been shown to play a role in oral cancer cell migration, invasion, and metastasis. Last but not least, we will present targeting strategies that have been developed to interfere with the function of some of these RBPs.

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Section: Introductionmentioning

confidence: 99%

RNA-Binding Proteins as Regulators of Migration, Invasion and Metastasis in Oral Squamous Cell Carcinoma

Weiße

Rosemann

Krauspe

et al. 2020

IJMS

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“…We analyzed the published datasets ( Cook and Vanderhyden, 2020 ) with ovarian OVCA420 cancer cell line capable of undergoing EMT. This cell line, which normally shows an epithelial morphology, was exposed to known EMT-inducing factors: TGFB1, EGF, and TNF, respectively, to promote EMT.…”

Section: Resultsmentioning

confidence: 99%

“…We started with trajectory reconstruction on the time-series datasets of an OVCA420 cancer cell line undergoing EMT induced by three different external signal (TGFB1, EGF, and TNF) and uncovered the existence of multiple ICSs displaying hybrid epithelial and mesenchymal features. Analysis of scRNA-seq previously demonstrated that EMT induction by TGFB1, EGF, and TNF is carried by context-specific signaling pathways ( Cook and Vanderhyden, 2020 ). Here, we show striking differences in the EMT population dynamics as well.…”

Section: Discussionmentioning

confidence: 99%

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Inference of Intercellular Communications and Multilayer Gene-Regulations of Epithelial–Mesenchymal Transition From Single-Cell Transcriptomic Data

et al. 2021

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Epithelial-to-mesenchymal transition (EMT) plays an important role in many biological processes during development and cancer. The advent of single-cell transcriptome sequencing techniques allows the dissection of dynamical details underlying EMT with unprecedented resolution. Despite several single-cell data analysis on EMT, how cell communicates and regulates dynamics along the EMT trajectory remains elusive. Using single-cell transcriptomic datasets, here we infer the cell–cell communications and the multilayer gene–gene regulation networks to analyze and visualize the complex cellular crosstalk and the underlying gene regulatory dynamics along EMT. Combining with trajectory analysis, our approach reveals the existence of multiple intermediate cell states (ICSs) with hybrid epithelial and mesenchymal features. Analyses on the time-series datasets from cancer cell lines with different inducing factors show that the induced EMTs are context-specific: the EMT induced by transforming growth factor B1 (TGFB1) is synchronous, whereas the EMTs induced by epidermal growth factor and tumor necrosis factor are asynchronous, and the responses of TGF-β pathway in terms of gene expression regulations are heterogeneous under different treatments or among various cell states. Meanwhile, network topology analysis suggests that the ICSs during EMT serve as the signaling in cellular communication under different conditions. Interestingly, our analysis of a mouse skin squamous cell carcinoma dataset also suggests regardless of the significant discrepancy in concrete genes between in vitro and in vivo EMT systems, the ICSs play dominant role in the TGF-β signaling crosstalk. Overall, our approach reveals the multiscale mechanisms coupling cell–cell communications and gene–gene regulations responsible for complex cell-state transitions.

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“…These scores, and scRNA-seq across a range of cancer cell lines, indicate a continuum in the gene expression landscape of EMP in both tumours and cell lines [Cursons et al, 2018, Karacosta et al, 2019a, Cook and Vanderhyden, 2020]. Given that EMP often involves changes in cellular morphology too, an EMP continuum in the morphological landscape is also being increasingly characterized recently [Leggett et al, 2016 The term metastable state was coined to describe the instability of these E/M hybrid cells [Klymkowsky andSavagner, 2009, Jia et al, 2018], although it may not apply equally to all E/M hybrids.…”

Section: Figure 1: Emp and The E/m Hybrid State Schematic Representamentioning

confidence: 99%

Measuring and Modelling the Epithelial Mesenchymal Hybrid State in Cancer: Clinical Implications

Jolly

Murphy

Bhatia

et al. 2020

Preprint

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The epithelial-mesenchymal (E/M) hybrid state has emerged as an important mediator of the elements of cancer progression facilitated by epithelial mesenchymal plasticity (EMP). We review here the evidence for the presence and prognostic potential of E/M hybrid state in carcinoma, modelling predictions and validations studies to demonstrate stabilised E/M hybrid intermediates along the spectrum of EMP, and computational approaches for characterising and quantifying EMP phenotypes, with particular attention to the emerging realm of single-cell approaches through RNA sequencing and protein-based approaches.

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Context specificity of the EMT transcriptional response

Cited by 193 publications

References 62 publications

RNA-Binding Proteins as Regulators of Migration, Invasion and Metastasis in Oral Squamous Cell Carcinoma

RNA-Binding Proteins as Regulators of Migration, Invasion and Metastasis in Oral Squamous Cell Carcinoma

Inference of Intercellular Communications and Multilayer Gene-Regulations of Epithelial–Mesenchymal Transition From Single-Cell Transcriptomic Data

Measuring and Modelling the Epithelial Mesenchymal Hybrid State in Cancer: Clinical Implications

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