Inactivation of Capicua drives cancer metastasis.
Authors | |
Abstract | Metastasis is the leading cause of death in people with lung cancer, yet the molecular effectors underlying tumor dissemination remain poorly defined. Through the development of an in vivo spontaneous lung cancer metastasis model, we show that the developmentally regulated transcriptional repressor Capicua (CIC) suppresses invasion and metastasis. Inactivation of CIC relieves repression of its effector ETV4, driving ETV4-mediated upregulation of MMP24, which is necessary and sufficient for metastasis. Loss of CIC, or an increase in levels of its effectors ETV4 and MMP24, is a biomarker of tumor progression and worse outcomes in people with lung and/or gastric cancer. Our findings reveal CIC as a conserved metastasis suppressor, highlighting new anti-metastatic strategies that could potentially improve patient outcomes. |
Year of Publication | 2017
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Journal | Nat Genet
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Volume | 49
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Issue | 1
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Pages | 87-96
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Date Published | 2017 Jan
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ISSN | 1546-1718
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DOI | 10.1038/ng.3728
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PubMed ID | 27869830
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PubMed Central ID | PMC5195898
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Links | |
Grant list | DP2 CA174497 / CA / NCI NIH HHS / United States
R01 CA169338 / CA / NCI NIH HHS / United States
T32 CA177555 / CA / NCI NIH HHS / United States
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