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Roles for growth factors and mutations in metastatic dissemination
Cancer is initiated largely by specific cohorts of genetic aberrations, which are generated by mutagens and often mimic active growth factor receptors, or downstream effectors. Once initiated cells outgrow and attract blood vessels, a multi-step process, called metastasis, disseminates cancer cells...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286841/ https://www.ncbi.nlm.nih.gov/pubmed/34100888 http://dx.doi.org/10.1042/BST20210048 |
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author | Nataraj, Nishanth Belugali Marrocco, Ilaria Yarden, Yosef |
author_facet | Nataraj, Nishanth Belugali Marrocco, Ilaria Yarden, Yosef |
author_sort | Nataraj, Nishanth Belugali |
collection | PubMed |
description | Cancer is initiated largely by specific cohorts of genetic aberrations, which are generated by mutagens and often mimic active growth factor receptors, or downstream effectors. Once initiated cells outgrow and attract blood vessels, a multi-step process, called metastasis, disseminates cancer cells primarily through vascular routes. The major steps of the metastatic cascade comprise intravasation into blood vessels, circulation as single or collectives of cells, and eventual colonization of distant organs. Herein, we consider metastasis as a multi-step process that seized principles and molecular players employed by physiological processes, such as tissue regeneration and migration of neural crest progenitors. Our discussion contrasts the irreversible nature of mutagenesis, which establishes primary tumors, and the reversible epigenetic processes (e.g. epithelial–mesenchymal transition) underlying the establishment of micro-metastases and secondary tumors. Interestingly, analyses of sequencing data from untreated metastases inferred depletion of putative driver mutations among metastases, in line with the pivotal role played by growth factors and epigenetic processes in metastasis. Conceivably, driver mutations may not confer the same advantage in the microenvironment of the primary tumor and of the colonization site, hence phenotypic plasticity rather than rigid cellular states hardwired by mutations becomes advantageous during metastasis. We review the latest reported examples of growth factors harnessed by the metastatic cascade, with the goal of identifying opportunities for anti-metastasis interventions. In summary, because the overwhelming majority of cancer-associated deaths are caused by metastatic disease, understanding the complexity of metastasis, especially the roles played by growth factors, is vital for preventing, diagnosing and treating metastasis. |
format | Online Article Text |
id | pubmed-8286841 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82868412021-08-02 Roles for growth factors and mutations in metastatic dissemination Nataraj, Nishanth Belugali Marrocco, Ilaria Yarden, Yosef Biochem Soc Trans Review Articles Cancer is initiated largely by specific cohorts of genetic aberrations, which are generated by mutagens and often mimic active growth factor receptors, or downstream effectors. Once initiated cells outgrow and attract blood vessels, a multi-step process, called metastasis, disseminates cancer cells primarily through vascular routes. The major steps of the metastatic cascade comprise intravasation into blood vessels, circulation as single or collectives of cells, and eventual colonization of distant organs. Herein, we consider metastasis as a multi-step process that seized principles and molecular players employed by physiological processes, such as tissue regeneration and migration of neural crest progenitors. Our discussion contrasts the irreversible nature of mutagenesis, which establishes primary tumors, and the reversible epigenetic processes (e.g. epithelial–mesenchymal transition) underlying the establishment of micro-metastases and secondary tumors. Interestingly, analyses of sequencing data from untreated metastases inferred depletion of putative driver mutations among metastases, in line with the pivotal role played by growth factors and epigenetic processes in metastasis. Conceivably, driver mutations may not confer the same advantage in the microenvironment of the primary tumor and of the colonization site, hence phenotypic plasticity rather than rigid cellular states hardwired by mutations becomes advantageous during metastasis. We review the latest reported examples of growth factors harnessed by the metastatic cascade, with the goal of identifying opportunities for anti-metastasis interventions. In summary, because the overwhelming majority of cancer-associated deaths are caused by metastatic disease, understanding the complexity of metastasis, especially the roles played by growth factors, is vital for preventing, diagnosing and treating metastasis. Portland Press Ltd. 2021-06-30 2021-06-08 /pmc/articles/PMC8286841/ /pubmed/34100888 http://dx.doi.org/10.1042/BST20210048 Text en © 2021 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Review Articles Nataraj, Nishanth Belugali Marrocco, Ilaria Yarden, Yosef Roles for growth factors and mutations in metastatic dissemination |
title | Roles for growth factors and mutations in metastatic dissemination |
title_full | Roles for growth factors and mutations in metastatic dissemination |
title_fullStr | Roles for growth factors and mutations in metastatic dissemination |
title_full_unstemmed | Roles for growth factors and mutations in metastatic dissemination |
title_short | Roles for growth factors and mutations in metastatic dissemination |
title_sort | roles for growth factors and mutations in metastatic dissemination |
topic | Review Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286841/ https://www.ncbi.nlm.nih.gov/pubmed/34100888 http://dx.doi.org/10.1042/BST20210048 |
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