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Inactivation of Capicua drives cancer metastasis

Metastasis is the leading cause of death in lung cancer patients, yet the molecular effectors underlying tumor dissemination remain poorly defined. Through development of an in vivo spontaneous lung cancer metastasis model, we show that the developmentally-regulated transcriptional repressor Capicua...

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Autores principales: Okimoto, Ross A., Breitenbuecher, Frank, Olivas, Victor R., Wu, Wei, Gini, Beatrice, Hofree, Matan, Asthana, Saurabh, Hrustanovic, Gorjan, Flanagan, Jennifer, Tulpule, Asmin, Blakely, Collin M., Haringsma, Henry J., Simmons, Andrew D., Gowen, Kyle, Suh, James, Miller, Vincent A., Ali, Siraj, Schuler, Martin, Bivona, Trever G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5195898/
https://www.ncbi.nlm.nih.gov/pubmed/27869830
http://dx.doi.org/10.1038/ng.3728
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author Okimoto, Ross A.
Breitenbuecher, Frank
Olivas, Victor R.
Wu, Wei
Gini, Beatrice
Hofree, Matan
Asthana, Saurabh
Hrustanovic, Gorjan
Flanagan, Jennifer
Tulpule, Asmin
Blakely, Collin M.
Haringsma, Henry J.
Simmons, Andrew D.
Gowen, Kyle
Suh, James
Miller, Vincent A.
Ali, Siraj
Schuler, Martin
Bivona, Trever G.
author_facet Okimoto, Ross A.
Breitenbuecher, Frank
Olivas, Victor R.
Wu, Wei
Gini, Beatrice
Hofree, Matan
Asthana, Saurabh
Hrustanovic, Gorjan
Flanagan, Jennifer
Tulpule, Asmin
Blakely, Collin M.
Haringsma, Henry J.
Simmons, Andrew D.
Gowen, Kyle
Suh, James
Miller, Vincent A.
Ali, Siraj
Schuler, Martin
Bivona, Trever G.
author_sort Okimoto, Ross A.
collection PubMed
description Metastasis is the leading cause of death in lung cancer patients, yet the molecular effectors underlying tumor dissemination remain poorly defined. Through development of an in vivo spontaneous lung cancer metastasis model, we show that the developmentally-regulated transcriptional repressor Capicua (CIC) suppresses invasion and metastasis. CIC inactivation relieves repression of its effector ETV4, driving ETV4-mediated upregulation of MMP24 that is necessary and sufficient for metastasis. Loss of CIC, or increased levels of its effectors ETV4 and MMP24, is a biomarker of tumor progression and worse outcomes in lung and gastric cancer patients. Our findings uncover CIC as a conserved metastasis suppressor, revealing new anti-metastatic strategies to improve patient outcomes.
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spelling pubmed-51958982017-05-21 Inactivation of Capicua drives cancer metastasis Okimoto, Ross A. Breitenbuecher, Frank Olivas, Victor R. Wu, Wei Gini, Beatrice Hofree, Matan Asthana, Saurabh Hrustanovic, Gorjan Flanagan, Jennifer Tulpule, Asmin Blakely, Collin M. Haringsma, Henry J. Simmons, Andrew D. Gowen, Kyle Suh, James Miller, Vincent A. Ali, Siraj Schuler, Martin Bivona, Trever G. Nat Genet Article Metastasis is the leading cause of death in lung cancer patients, yet the molecular effectors underlying tumor dissemination remain poorly defined. Through development of an in vivo spontaneous lung cancer metastasis model, we show that the developmentally-regulated transcriptional repressor Capicua (CIC) suppresses invasion and metastasis. CIC inactivation relieves repression of its effector ETV4, driving ETV4-mediated upregulation of MMP24 that is necessary and sufficient for metastasis. Loss of CIC, or increased levels of its effectors ETV4 and MMP24, is a biomarker of tumor progression and worse outcomes in lung and gastric cancer patients. Our findings uncover CIC as a conserved metastasis suppressor, revealing new anti-metastatic strategies to improve patient outcomes. 2016-11-21 2017-01 /pmc/articles/PMC5195898/ /pubmed/27869830 http://dx.doi.org/10.1038/ng.3728 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Okimoto, Ross A.
Breitenbuecher, Frank
Olivas, Victor R.
Wu, Wei
Gini, Beatrice
Hofree, Matan
Asthana, Saurabh
Hrustanovic, Gorjan
Flanagan, Jennifer
Tulpule, Asmin
Blakely, Collin M.
Haringsma, Henry J.
Simmons, Andrew D.
Gowen, Kyle
Suh, James
Miller, Vincent A.
Ali, Siraj
Schuler, Martin
Bivona, Trever G.
Inactivation of Capicua drives cancer metastasis
title Inactivation of Capicua drives cancer metastasis
title_full Inactivation of Capicua drives cancer metastasis
title_fullStr Inactivation of Capicua drives cancer metastasis
title_full_unstemmed Inactivation of Capicua drives cancer metastasis
title_short Inactivation of Capicua drives cancer metastasis
title_sort inactivation of capicua drives cancer metastasis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5195898/
https://www.ncbi.nlm.nih.gov/pubmed/27869830
http://dx.doi.org/10.1038/ng.3728
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