Chromatin Remodeling of Colorectal Cancer Liver Metastasis is Mediated by an HGF-PU.1-DPP4 Axis.


Colorectal cancer (CRC) metastasizes mainly to the liver, which accounts for the majority of CRC-related deaths. Here it is shown that metastatic cells undergo specific chromatin remodeling in the liver. Hepatic growth factor (HGF) induces phosphorylation of PU.1, a pioneer factor, which in turn binds and opens chromatin regions of downstream effector genes. PU.1 increases histone acetylation at the DPP4 locus. Precise epigenetic silencing by CRISPR/dCas9KRAB or CRISPR/dCas9HDAC revealed that individual PU.1-remodeled regulatory elements collectively modulate DPP4 expression and liver metastasis growth. Genetic silencing or pharmacological inhibition of each factor along this chromatin remodeling axis strongly suppressed liver metastasis. Therefore, microenvironment-induced epimutation is an important mechanism for metastatic tumor cells to grow in their new niche. This study presents a potential strategy to target chromatin remodeling in metastatic cancer and the promise of repurposing drugs to treat metastasis.





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Publication Info

Wang, Lihua, Ergang Wang, Jorge Prado Balcazar, Zhenzhen Wu, Kun Xiang, Yi Wang, Qiang Huang, Marcos Negrete, et al. (2021). Chromatin Remodeling of Colorectal Cancer Liver Metastasis is Mediated by an HGF-PU.1-DPP4 Axis. Advanced science (Weinheim, Baden-Wurttemberg, Germany), 8(19). p. e2004673. 10.1002/advs.202004673 Retrieved from

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Purushothama Rao Tata

Associate Professor of Cell Biology

Lung regeneration
Lung stem cells
Cell plasticity
Organoid models
Lung Fibrosis
Single Cell Biology


Charles Gersbach

John W. Strohbehn Distinguished Professor of Biomedical Engineering

Gregory E. Crawford

Professor in Pediatrics

My primary research interest is understanding how the genome is regulated.  The human genome contains approximately 25,000 genes, which are encoded in ~2% of the genome. The overarching goal of my research program is to identify and characterize how these genes are turned on and off in different cell types, tissues, development states, environmental responses, diseases, and individuals. By understanding where all gene regulatory elements are located, how they work to regulate gene expression, and how non-coding variants within these regions affect function, my research program can address a number of important basic and clinical questions.


Xiling Shen

Adjunct Professor in the Department of Pathology

Dr. Shen’s research interests lie at precision medicine and systems biology. His lab integrates engineering, computational and biological techniques to study cancer, stem cells, microbiota and the nervous system in the gut. This multidisciplinary work has been instrumental in initiating several translational clinical trials in precision therapy. He is the director of the Woo Center for Big Data and Precision Health (DAP) and a core member of the Center for Genomics and Computational Biology (GCB).

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