The landscape of EMT (epithelial- mesenchymal transitions), the role of epigenetics, and the relevance for cancer metastasis

Abstract: The emergence of and transitions between distinct phenotypes in cancer cells undergoing epithelial-mesenchymal transition (EMT) can be attributed to the intricate interplay of epigenetic marks, external signals, and gene regulatory elements. In particular, recent analysis of RNA-seq data shows that the choice of phenotype adopted by a cell undergoing EMT is strongly influenced by epigenetic factors. Mathematical models known as Gene Regulatory Networks (GRNs) are an increasingly important tool to unravel the workings of such complex networks. In such models, epigenetic factors are usually proposed to act on the chromatin regions directly involved in the expression of relevant genes. However, it has been well-established that these factors operate globally and compete with each other for targets genome-wide. We propose a conceptual and mathematical modeling framework that incorporates both local and global competition effects between antagonistic epigenetic regulators in addition to local transcription factors, and show the counter-intuitive consequences of such interactions. We apply our approach to recent experimental data.

Bio: Dr. Herbert Levine is a University Distinguished Professor in Physics and Bioengineering Departments at Northeastern University. He is also a co-director of an NSF frontier center on Theoretical Biological Physics. His recent interests involve the physical modeling of cancer progression, metastasis, and interaction with the immune system. He is an American Physical Society fellow, and a member of the National Academy of Sciences and the American Academy of Arts and Sciences.