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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Detalles Bibliográficos
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:
Article
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
Descripción
Sumario: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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