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Hypoxia, partial EMT and collective migration: Emerging culprits in metastasis
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 a successful colonization at the...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Neoplasia Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419667/ https://www.ncbi.nlm.nih.gov/pubmed/32781367 http://dx.doi.org/10.1016/j.tranon.2020.100845 |
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author | Saxena, Kritika Jolly, Mohit Kumar Balamurugan, Kuppusamy |
author_facet | Saxena, Kritika Jolly, Mohit Kumar Balamurugan, Kuppusamy |
author_sort | Saxena, Kritika |
collection | PubMed |
description | 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 a successful colonization at the distant site. EMT is not a binary process; recent evidence suggests that cells in partial EMT or hybrid E/M phenotype(s) can have enhanced stemness and drug resistance as compared to those undergoing a complete EMT. Moreover, partial EMT enables collective migration of cells as clusters of circulating tumor cells or emboli, further endorsing that cells in hybrid E/M phenotypes may be the ‘fittest’ for metastasis. Here, we review mechanisms and implications of hybrid E/M phenotypes, including their reported association with hypoxia. Hypoxia-driven activation of HIF-1α can drive EMT. In addition, cyclic hypoxia, as compared to acute or chronic hypoxia, shows the highest levels of active HIF-1α and can augment cancer aggressiveness to a greater extent, including enriching for a partial EMT phenotype. We also discuss how metastasis is influenced by hypoxia, partial EMT and collective cell migration, and call for a better understanding of interconnections among these mechanisms. We discuss the known regulators of hypoxia, hybrid EMT and collective cell migration and highlight the gaps which needs to be filled for connecting these three axes which will increase our understanding of dynamics of metastasis and help control it more effectively. |
format | Online Article Text |
id | pubmed-7419667 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Neoplasia Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-74196672020-08-14 Hypoxia, partial EMT and collective migration: Emerging culprits in metastasis Saxena, Kritika Jolly, Mohit Kumar Balamurugan, Kuppusamy Transl Oncol Review article 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 a successful colonization at the distant site. EMT is not a binary process; recent evidence suggests that cells in partial EMT or hybrid E/M phenotype(s) can have enhanced stemness and drug resistance as compared to those undergoing a complete EMT. Moreover, partial EMT enables collective migration of cells as clusters of circulating tumor cells or emboli, further endorsing that cells in hybrid E/M phenotypes may be the ‘fittest’ for metastasis. Here, we review mechanisms and implications of hybrid E/M phenotypes, including their reported association with hypoxia. Hypoxia-driven activation of HIF-1α can drive EMT. In addition, cyclic hypoxia, as compared to acute or chronic hypoxia, shows the highest levels of active HIF-1α and can augment cancer aggressiveness to a greater extent, including enriching for a partial EMT phenotype. We also discuss how metastasis is influenced by hypoxia, partial EMT and collective cell migration, and call for a better understanding of interconnections among these mechanisms. We discuss the known regulators of hypoxia, hybrid EMT and collective cell migration and highlight the gaps which needs to be filled for connecting these three axes which will increase our understanding of dynamics of metastasis and help control it more effectively. Neoplasia Press 2020-08-08 /pmc/articles/PMC7419667/ /pubmed/32781367 http://dx.doi.org/10.1016/j.tranon.2020.100845 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Review article Saxena, Kritika Jolly, Mohit Kumar Balamurugan, Kuppusamy Hypoxia, partial EMT and collective migration: Emerging culprits in metastasis |
title | Hypoxia, partial EMT and collective migration: Emerging culprits in metastasis |
title_full | Hypoxia, partial EMT and collective migration: Emerging culprits in metastasis |
title_fullStr | Hypoxia, partial EMT and collective migration: Emerging culprits in metastasis |
title_full_unstemmed | Hypoxia, partial EMT and collective migration: Emerging culprits in metastasis |
title_short | Hypoxia, partial EMT and collective migration: Emerging culprits in metastasis |
title_sort | hypoxia, partial emt and collective migration: emerging culprits in metastasis |
topic | Review article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419667/ https://www.ncbi.nlm.nih.gov/pubmed/32781367 http://dx.doi.org/10.1016/j.tranon.2020.100845 |
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