Dataset Information

New Insights Into the Role of Phenotypic Plasticity and EMT in Driving Cancer Progression.

ABSTRACT: Tumor cells demonstrate substantial plasticity in their genotypic and phenotypic characteristics. Epithelial-mesenchymal plasticity (EMP) can be characterized into dynamic intermediate states and can be orchestrated by many factors, either intercellularly via epigenetic reprograming, or extracellularly via growth factors, inflammation and/or hypoxia generated by the tumor stromal microenvironment. EMP has the capability to alter phenotype and produce heterogeneity, and thus by changing the whole cancer landscape can attenuate oncogenic signaling networks, invoke anti-apoptotic features, defend against chemotherapeutics and reprogram angiogenic and immune recognition functions. We discuss here the role of phenotypic plasticity in tumor initiation, progression and metastasis and provide an update of the modalities utilized for the molecular characterization of the EMT states and attributes of cellular behavior, including cellular metabolism, in the context of EMP. We also summarize recent findings in dynamic EMP studies that provide new insights into the phenotypic plasticity of EMP flux in cancer and propose therapeutic strategies to impede the metastatic outgrowth of phenotypically heterogeneous tumors.

SUBMITTER: Bhatia S

PROVIDER: S-EPMC7190792 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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New Insights Into the Role of Phenotypic Plasticity and EMT in Driving Cancer Progression.

Bhatia Sugandha S Wang Peiyu P Toh Alan A Thompson Erik W EW

Frontiers in molecular biosciences 20200423

Tumor cells demonstrate substantial plasticity in their genotypic and phenotypic characteristics. Epithelial-mesenchymal plasticity (EMP) can be characterized into dynamic intermediate states and can be orchestrated by many factors, either intercellularly via epigenetic reprograming, or extracellularly via growth factors, inflammation and/or hypoxia generated by the tumor stromal microenvironment. EMP has the capability to alter phenotype and produce heterogeneity, and thus by changing the whole ...[more]

PMID: 32391381

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Project description:Waddington's epigenetic landscape, a famous metaphor in developmental biology, depicts how a stem cell progresses from an undifferentiated phenotype to a differentiated one. The concept of "landscape" in the context of dynamical systems theory represents a high-dimensional space, in which each cell phenotype is considered as an "attractor" that is determined by interactions between multiple molecular players, and is buffered against environmental fluctuations. In addition, biological noise is thought to play an important role during these cell-fate decisions and in fact controls transitions between different phenotypes. Here, we discuss the phenotypic transitions in cancer from a dynamical systems perspective and invoke the concept of "cancer attractors"-hidden stable states of the underlying regulatory network that are not occupied by normal cells. Phenotypic transitions in cancer occur at varying levels depending on the context. Using epithelial-to-mesenchymal transition (EMT), cancer stem-like properties, metabolic reprogramming and the emergence of therapy resistance as examples, we illustrate how phenotypic plasticity in cancer cells enables them to acquire hybrid phenotypes (such as hybrid epithelial/mesenchymal and hybrid metabolic phenotypes) that tend to be more aggressive and notoriously resilient to therapies such as chemotherapy and androgen-deprivation therapy. Furthermore, we highlight multiple factors that may give rise to phenotypic plasticity in cancer cells, such as (a) multi-stability or oscillatory behaviors governed by underlying regulatory networks involved in cell-fate decisions in cancer cells, and (b) network rewiring due to conformational dynamics of intrinsically disordered proteins (IDPs) that are highly enriched in cancer cells. We conclude by discussing why a therapeutic approach that promotes "recanalization", i.e., the exit from "cancer attractors" and re-entry into "normal attractors", is more likely to succeed rather than a conventional approach that targets individual molecules/pathways.

Dataset Information

New Insights Into the Role of Phenotypic Plasticity and EMT in Driving Cancer Progression.

Publications

New Insights Into the Role of Phenotypic Plasticity and EMT in Driving Cancer Progression.

Similar Datasets

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