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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...

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Detalles Bibliográficos
Autores principales: Nataraj, Nishanth Belugali, Marrocco, Ilaria, Yarden, Yosef
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2021
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.
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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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