Starvation and pseudo-starvation as drivers of cancer metastasis through translation reprogramming

Considerable progress has been made in identifying microenvironmental signals that effect the reversible phenotypic transitions underpinning the early steps in the metastatic cascade. However, although the general principles underlying metastatic dissemination have been broadly outlined, a common th...

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Autores principales: Garcia-Jimenez, C, Goding, C
Formato: Journal article
Publicado: Elsevier 2018
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author Garcia-Jimenez, C
Goding, C
author_facet Garcia-Jimenez, C
Goding, C
author_sort Garcia-Jimenez, C
collection OXFORD
description Considerable progress has been made in identifying microenvironmental signals that effect the reversible phenotypic transitions underpinning the early steps in the metastatic cascade. However, although the general principles underlying metastatic dissemination have been broadly outlined, a common theme that unifies many of the triggers of invasive behavior in tumors has yet to emerge. Here we discuss how many diverse signals that induce invasion converge on the reprogramming of protein translation via phosphorylation of eIF2α, a hallmark of the starvation response. These include starvation as a consequence of nutrient or oxygen limitation, or pseudo-starvation imposed by cell-extrinsic microenvironmental signals or by cell-intrinsic events, including oncogene activation. Since in response to resource limitation single-cell organisms undergo phenotypic transitions remarkably similar to those observed within tumors, we propose that a starvation/pseudo-starvation model to explain cancer progression provides an integrated and evolutionarily conserved conceptual framework to understand the progression of this complex disease.
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spelling oxford-uuid:f0242602-d1e1-47fc-bd7c-dce4d1cc57532022-03-27T11:45:35ZStarvation and pseudo-starvation as drivers of cancer metastasis through translation reprogrammingJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f0242602-d1e1-47fc-bd7c-dce4d1cc5753Symplectic Elements at OxfordElsevier2018Garcia-Jimenez, CGoding, CConsiderable progress has been made in identifying microenvironmental signals that effect the reversible phenotypic transitions underpinning the early steps in the metastatic cascade. However, although the general principles underlying metastatic dissemination have been broadly outlined, a common theme that unifies many of the triggers of invasive behavior in tumors has yet to emerge. Here we discuss how many diverse signals that induce invasion converge on the reprogramming of protein translation via phosphorylation of eIF2α, a hallmark of the starvation response. These include starvation as a consequence of nutrient or oxygen limitation, or pseudo-starvation imposed by cell-extrinsic microenvironmental signals or by cell-intrinsic events, including oncogene activation. Since in response to resource limitation single-cell organisms undergo phenotypic transitions remarkably similar to those observed within tumors, we propose that a starvation/pseudo-starvation model to explain cancer progression provides an integrated and evolutionarily conserved conceptual framework to understand the progression of this complex disease.
spellingShingle Garcia-Jimenez, C
Goding, C
Starvation and pseudo-starvation as drivers of cancer metastasis through translation reprogramming
title Starvation and pseudo-starvation as drivers of cancer metastasis through translation reprogramming
title_full Starvation and pseudo-starvation as drivers of cancer metastasis through translation reprogramming
title_fullStr Starvation and pseudo-starvation as drivers of cancer metastasis through translation reprogramming
title_full_unstemmed Starvation and pseudo-starvation as drivers of cancer metastasis through translation reprogramming
title_short Starvation and pseudo-starvation as drivers of cancer metastasis through translation reprogramming
title_sort starvation and pseudo starvation as drivers of cancer metastasis through translation reprogramming
work_keys_str_mv AT garciajimenezc starvationandpseudostarvationasdriversofcancermetastasisthroughtranslationreprogramming
AT godingc starvationandpseudostarvationasdriversofcancermetastasisthroughtranslationreprogramming