Network of mutually repressive metastasis regulators can promote cell heterogeneity and metastatic transitions
-
- Jiyoung Lee
- Ben May Department for Cancer Research, The University of Chicago, Chicago, IL 60637;
-
- Jinho Lee
- Department of Systems Biology–Unit 950, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054;
-
- Kevin S. Farquhar
- Department of Systems Biology–Unit 950, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054;
-
- Jieun Yun
- Ben May Department for Cancer Research, The University of Chicago, Chicago, IL 60637;
-
- Casey A. Frankenberger
- Ben May Department for Cancer Research, The University of Chicago, Chicago, IL 60637;
-
- Elena Bevilacqua
- Ben May Department for Cancer Research, The University of Chicago, Chicago, IL 60637;
-
- Kam Yeung
- Department of Biochemistry and Cancer Biology, The University of Toledo, Toledo, OH 43606; and
-
- Eun-Jin Kim
- School of Mathematics and Statistics, University of Sheffield, Sheffield S3 7RH, United Kingdom
-
- Gábor Balázsi
- Department of Systems Biology–Unit 950, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054;
-
- Marsha Rich Rosner
- Ben May Department for Cancer Research, The University of Chicago, Chicago, IL 60637;
説明
<jats:title>Significance</jats:title> <jats:p>Cancer progression, as an evolutionary process, should accelerate if higher cellular variability is present. However, the sources of nongenetic variability in metastatic progression are largely unknown. To address this question, we characterized a transcriptional regulatory network for the metastasis suppressor Raf kinase inhibitory protein (RKIP). We previously showed that the transcription factor BACH1 is negatively regulated by RKIP and promotes breast cancer metastasis. Here we reveal a network architecture between the metastasis suppressor RKIP and the metastasis promoter BACH1 that enables single cells to generate a stable subpopulation of prometastatic cells without any genetic changes.</jats:p>
収録刊行物
-
- Proceedings of the National Academy of Sciences
-
Proceedings of the National Academy of Sciences 111 (3), E364-, 2014-01-06
Proceedings of the National Academy of Sciences
