Acute vs. Chronic vs. Cyclic Hypoxia: Their Differential Dynamics, Molecular Mechanisms, and Effects on Tumor Progression

Biomolecules, Journal Year: 2019, Volume and Issue: 9(8), P. 339 - 339

Published: Aug. 3, 2019

Hypoxia has been shown to increase the aggressiveness and severity of tumor progression. Along with chronic acute hypoxic regions, solid tumors contain regions cycling hypoxia (also called intermittent or IH). Cyclic is mimicked in vitro vivo by periodic exposure cycles reoxygenation (H-R cycles). Compared hypoxia, cyclic augment various hallmarks cancer a greater extent: angiogenesis, immune evasion, metastasis, survival etc. Cycling also be major contributing factor increasing risk obstructive sleep apnea (OSA) patients. Here, we first compare contrast effects acute, terms molecular pathways activated cellular processes affected. We highlight underlying complexity these differential emphasize need investigate combinations factors impacting adaptation hypoxia: total duration concentration oxygen (O2), presence frequency H-R cycles. Finally, summarize on highlighting their dependence abovementioned factors. conclude call for an integrative rigorous analysis varying extents durations cells, including tools such as mechanism-based mathematical modelling microfluidic setups.

Language: Английский

---

Epigenetics as a mediator of plasticity in cancer

Science, Journal Year: 2023, Volume and Issue: 379(6632)

Published: Feb. 10, 2023

The concept of an epigenetic landscape describing potential cellular fates arising from pluripotent cells, first advanced by Conrad Waddington, has evolved in light experiments showing nondeterministic outcomes regulatory processes and mathematical methods for quantifying stochasticity. In this Review, we discuss modern approaches to gene regulation landscapes the associated ideas entropy attractor states, illustrating how their definitions are both more precise relevant understanding cancer etiology plasticity cancerous states. We address interplay between different types changes underlie progression. also consider roles aging intrinsic extrinsic stimuli modulating states alterations can be quantitatively mapped onto phenotypic thereby used therapy development.

Language: Английский

---

Hypoxia, partial EMT and collective migration: Emerging culprits in metastasis

Translational Oncology, Journal Year: 2020, Volume and Issue: 13(11), P. 100845 - 100845

Published: Aug. 8, 2020

Epithelial-mesenchymal transition (EMT) is a cellular biological process involved in migration of primary cancer cells to secondary sites facilitating metastasis. Besides, EMT also confers properties such as stemness, drug resistance and immune evasion which can aid successful colonization at the distant site. not binary process; recent evidence suggests that partial or hybrid E/M phenotype(s) have enhanced stemness compared those undergoing complete EMT. Moreover, enables collective clusters circulating tumor emboli, further endorsing phenotypes may be 'fittest' for Here, we review mechanisms implications phenotypes, including their reported association with hypoxia. Hypoxia-driven activation HIF-1α drive In addition, cyclic hypoxia, acute chronic shows highest levels active augment aggressiveness greater extent, enriching phenotype. We discuss how metastasis influenced by cell migration, call better understanding interconnections among these mechanisms. known regulators highlight gaps needs filled connecting three axes will increase our dynamics help control it more effectively.

Language: Английский

---

The epithelial–mesenchymal plasticity landscape: principles of design and mechanisms of regulation

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 24(9), P. 590 - 609

Published: May 11, 2023

Language: Английский

---

Cancer Stem Cells and Epithelial-to-Mesenchymal Transition in Cancer Metastasis

Cold Spring Harbor Perspectives in Medicine, Journal Year: 2019, Volume and Issue: 10(7), P. a036905 - a036905

Published: Sept. 30, 2019

Toni Celià-Terrassa1 and Mohit Kumar Jolly2 1Cancer Research Program, IMIM (Hospital del Mar Medical Institute), 08003 Barcelona, Spain 2Centre for BioSystems Science Engineering, Indian Institute of Science, Bangalore 560012, India Correspondence: acelia{at}imim.es; mkjolly{at}iisc.ac.in

Language: Английский

---

Dynamics of Phenotypic Heterogeneity Associated with EMT and Stemness during Cancer Progression

Journal of Clinical Medicine, Journal Year: 2019, Volume and Issue: 8(10), P. 1542 - 1542

Published: Sept. 25, 2019

Genetic and phenotypic heterogeneity contribute to the generation of diverse tumor cell populations, thus enhancing cancer aggressiveness therapy resistance. Compared genetic heterogeneity, a consequence mutational events, arises from dynamic, reversible state transitions in response varying intracellular/extracellular signals. Such plasticity enables rapid adaptive responses various stressful conditions can have strong impact on progression. Herein, we reviewed relevant literature mechanisms associated with dynamic changes cellular plasticity, such as epithelial–mesenchymal transition (EMT) stemness, which been reported facilitate metastasis. We also discuss how non-cell-autonomous cell–cell communication lead an emergent population-level tumors. The molecular underlying complexity systems are crucial for comprehending progression, may provide new avenues designing therapeutic strategies.

Language: Английский

---

Comparative Study of Transcriptomics-Based Scoring Metrics for the Epithelial-Hybrid-Mesenchymal Spectrum

Frontiers in Bioengineering and Biotechnology, Journal Year: 2020, Volume and Issue: 8

Published: March 20, 2020

The Epithelial-mesenchymal transition (EMT) is a cellular process implicated in embryonic development, wound healing, and pathological conditions such as cancer metastasis fibrosis. Cancer cells undergoing EMT exhibit enhanced aggressive behavior characterized by drug resistance, tumor-initiation potential, the ability to evade immune system. Recent silico, vitro, vivo evidence indicates that not an all-or-none process; instead, can stably acquire one or more hybrid epithelial/mesenchymal (E/M) phenotypes which often be than purely E M cell populations. Thus, status of prove critical estimate patient prognosis. attempts have employed different transcriptomics signatures quantify lines tumors. However, comprehensive comparison these methods, including their accuracy identifying E/M phenotype(s), lacking. Here, we compare three distinct metrics score on continuum, based signature individual samples. Our results demonstrate methods good concordance among themselves quantifying extent given sample. Moreover, scoring using any discerned undergo varying extents across tumor types. Separately, our analysis also identified types with maximum variability terms associated enrichment found multinomial logistic regression (MLR)-based metric was capable distinguishing between "pure" vs. mixtures cells. results, thus, suggest while indicate generic trend cell, MLR method has two additional advantages: (a) it uses small number predictors calculate (b) predict from transcriptomic population whether comprised at single-cell level instead ensemble subpopulations.

Language: Английский

---

Interplay between tumor microenvironment and partial EMT as the driver of tumor progression

iScience, Journal Year: 2021, Volume and Issue: 24(2), P. 102113 - 102113

Published: Jan. 28, 2021

Epithelial-to-mesenchymal transition (EMT), an evolutionary conserved phenomenon, has been extensively studied to address the unresolved variable treatment response across therapeutic regimes in cancer subtypes. EMT long envisaged regulate tumor invasion, migration, and resistance during tumorigenesis. However, recently it highlighted that involves intermediate partial (pEMT) phenotype, defined by incomplete loss of epithelial markers gain mesenchymal markers. It further emphasized pEMT a spectrum hybrid states on either side spectrum. Emerging evidence underlines bi-directional crosstalk between cells surrounding microenvironment acquisition phenotype. Although much work is still ongoing mechanistic insights into regulation evident plays critical role aggressiveness, metastasis along with resistance. In this review, we focus important tumor-intrinsic factors driving emphasize engineered controlled microenvironments are instrumental provide biology. We also discuss significance regulating hallmarks progression i.e. cell cycle regulation, collective constantly evolving, current progress momentum field holds promise unravel new targets halt at early stages as well tackle complex observed many types.

Language: Английский

---

Identifying inhibitors of epithelial–mesenchymal plasticity using a network topology-based approach

npj Systems Biology and Applications, Journal Year: 2020, Volume and Issue: 6(1)

Published: May 18, 2020

Metastasis is the cause of over 90% cancer-related deaths. Cancer cells undergoing metastasis can switch dynamically between different phenotypes, enabling them to adapt harsh challenges, such as overcoming anoikis and evading immune response. This ability, known phenotypic plasticity, crucial for survival cancer during metastasis, well acquiring therapy resistance. Various biochemical networks have been identified contribute but how plasticity emerges from dynamics these remains elusive. Here, we investigated various regulatory implicated in Epithelial-mesenchymal (EMP)-an important arm plasticity-through two mathematical modelling frameworks: a discrete, parameter-independent framework (Boolean) continuous, parameter-agnostic (RACIPE). Results either terms distributions obtained given EMP network are qualitatively similar suggest that multi-stable give rise plasticity. Neither method requires specific kinetic parameters, thus our results emphasize emerge through wide range parameter sets, elucidating importance topology Furthermore, show ability exhibit correlates positively with number positive feedback loops network. These pave way toward an unorthodox topology-based approach identify links reduce possibly inhibit metastasis-by reducing loops.

Language: Английский

---

Quantifying Cancer Epithelial-Mesenchymal Plasticity and its Association with Stemness and Immune Response

Journal of Clinical Medicine, Journal Year: 2019, Volume and Issue: 8(5), P. 725 - 725

Published: May 22, 2019

Cancer cells can acquire a spectrum of stable hybrid epithelial/mesenchymal (E/M) states during epithelial–mesenchymal transition (EMT). Cells in these E/M phenotypes often combine epithelial and mesenchymal features tend to migrate collectively commonly as small clusters. Such migrating cancer play pivotal role seeding metastases their presence patients indicates an adverse prognostic factor. Moreover, be more associated with stemness which endows them tumor-initiation ability therapy resistance. Most recently, undergoing EMT have been shown promote immune suppression for better survival. A systematic understanding the emergence connection would contribute effective therapeutic strategies. In this review, we first discuss recent efforts combining theoretical experimental approaches elucidate mechanisms underlying multi-stability (i.e., existence multiple EMT) properties phenotypes. Following non-cell-autonomous regulation by cell cooperation extracellular matrix. Afterwards, various metrics that used quantify spectrum. We further describe possible formation clusters circulating tumor cells. Last but not least, summarize systems biology analysis acquisition suppression.

Language: Английский

---