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

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The regulation of the homeostasis and regeneration of peripheral nerve is distinct from the CNS and independent of a stem cell population

Development, Journal Year: 2018, Volume and Issue: 145(24)

Published: Nov. 9, 2018

ABSTRACT Peripheral nerves are highly regenerative, in contrast to the poor regenerative capabilities of central nervous system (CNS). Here, we show that adult peripheral nerve is a more quiescent tissue than CNS, yet all cell types within proliferate efficiently following injury. Moreover, whereas oligodendrocytes produced throughout life from precursor pool, find corresponding system, myelinating Schwann (mSC), does not turn over adult. However, injury, mSCs can dedifferentiate proliferating progenitor-like cells (SCs) orchestrate response. Lineage analysis shows these newly migratory, redifferentiate form new at injury site and maintain their lineage, but switch become non-myelinating SC. In contrast, increased plasticity observed during tumourigenesis. These findings have distinct mechanism for maintaining homeostasis regenerate without need an additional stem population. This article has associated ‘The people behind papers’ interview.

Language: Английский

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Impact of the Tumor Microenvironment on Tumor Heterogeneity and Consequences for Cancer Cell Plasticity and Stemness

Cancers, Journal Year: 2020, Volume and Issue: 12(12), P. 3716 - 3716

Published: Dec. 11, 2020

Tumor heterogeneity is considered the major cause of treatment failure in current cancer therapies. This feature solid tumors not only result clonal outgrowth cells with genetic mutations, but also epigenetic alterations induced by physical and chemical signals from tumor microenvironment (TME). Besides fibroblasts, endothelial immune cells, mesenchymal stroma/stem-like (MSCs) tumor-associated macrophages (TAMs) intimately crosstalk can exhibit both anti- pro-tumorigenic effects. MSCs alter cellular phenotypes to increase cell plasticity, eventually resulting generation stem (CSCs). The shift between different phenotypic states (phenotype switching) CSCs controlled via programs, such as epithelial-mesenchymal transdifferentiation or retrodifferentiation, triggered TME, like hypoxia, spatial stromal cell-derived chemokines. Finally, we highlight role spontaneous fusion various types cells. i.e., shaping CSC plasticity. A better understanding plasticity phenotype shifting a prerequisite for exploiting this phenomenon reduce heterogeneity, thereby improving chance therapy success.

Language: Английский

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Nucleus-targeted nano delivery system eradicates cancer stem cells by combined thermotherapy and hypoxia-activated chemotherapy

Biomaterials, Journal Year: 2019, Volume and Issue: 200, P. 1 - 14

Published: Feb. 9, 2019

Language: Английский

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USP1 links platinum resistance to cancer cell dissemination by regulating Snail stability

Science Advances, Journal Year: 2019, Volume and Issue: 5(5)

Published: May 3, 2019

Resistance to platinum-based chemotherapy is a common event in patients with cancer, generally associated tumor dissemination and metastasis. Whether platinum treatment per se activates molecular pathways linked spreading not known. Here, we report that the ubiquitin-specific protease 1 (USP1) mediates ovarian cancer cell resistance platinum, by regulating stability of Snail, which, turn, promotes dissemination. At level, observed upon treatment, USP1 phosphorylated ATM ATR binds Snail. Then, de-ubiquitinates stabilizes Snail expression, conferring increased stem cell-like features, metastatic ability. Consistently, knockout or pharmacological inhibition sensitivity decreased Snail-dependent manner. Our findings identify as target open way novel strategy overcome more successfully treat cancer.

Language: Английский

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