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...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-11-01
|
| Series: | Translational Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523320303375 |
| _version_ | 1818457305799196672 |
|---|---|
| author | Kritika Saxena Mohit Kumar Jolly Kuppusamy Balamurugan |
| author_facet | Kritika Saxena Mohit Kumar Jolly Kuppusamy Balamurugan |
| author_sort | Kritika Saxena |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T22:40:28Z |
| format | Article |
| id | doaj.art-1e05588b99a44d52aadb9a059b9bff6f |
| institution | Directory Open Access Journal |
| issn | 1936-5233 |
| language | English |
| last_indexed | 2024-12-14T22:40:28Z |
| publishDate | 2020-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-1e05588b99a44d52aadb9a059b9bff6f2022-12-21T22:45:00ZengElsevierTranslational Oncology1936-52332020-11-011311100845Hypoxia, partial EMT and collective migration: Emerging culprits in metastasisKritika Saxena0Mohit Kumar Jolly1Kuppusamy Balamurugan2Centre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore 560012, IndiaCentre for BioSystems Science and Engineering, Indian Institute of Science, Bangalore 560012, India; Corresponding authors.Laboratory of Cell and Developmental Signaling, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA; Corresponding authors.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.http://www.sciencedirect.com/science/article/pii/S1936523320303375HIF-1αpartial EMTCollective migrationInflammatory breast cancerMetastasis |
| spellingShingle | Kritika Saxena Mohit Kumar Jolly Kuppusamy Balamurugan Hypoxia, partial EMT and collective migration: Emerging culprits in metastasis Translational Oncology HIF-1α partial EMT Collective migration Inflammatory breast cancer 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 | HIF-1α partial EMT Collective migration Inflammatory breast cancer Metastasis |
| url | http://www.sciencedirect.com/science/article/pii/S1936523320303375 |
| work_keys_str_mv | AT kritikasaxena hypoxiapartialemtandcollectivemigrationemergingculpritsinmetastasis AT mohitkumarjolly hypoxiapartialemtandcollectivemigrationemergingculpritsinmetastasis AT kuppusamybalamurugan hypoxiapartialemtandcollectivemigrationemergingculpritsinmetastasis |