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Title: | Chromatin Remodeling of Colorectal Cancer Liver Metastasis is Mediated by an HGF‐PU.1‐DPP4 Axis |
Author: | Wang, Lihua Wang, Ergang Prado Balcazar, Jorge Wu, Zhenzhen Xiang, Kun Wang, Yi Huang, Qiang Negrete, Marcos Chen, Kai‐yuan Li, Wei Fu, Yujie Dohlman, Anders Mines, Robert Zhang, Liwen Kobayashi, Yoshihiko Chen, Tianyi Shi, Guizhi Shen, John Paul Kopetz, Scott Tata, Purushothama Rao Moreno Aguado, Víctor Gersbach, Charles Crawford, Gregory Hsu, David Huang, Emina Bu, Pengcheng Shen, Xiling |
Keywords: | Càncer colorectal Metàstasi Colorectal cancer Metastasis |
Issue Date: | 10-Aug-2021 |
Publisher: | Wiley |
Abstract: | 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1002/advs.202004673 |
It is part of: | Advanced Science, 2021, vol. 8, p. 2004673 |
URI: | http://hdl.handle.net/2445/179937 |
Related resource: | https://doi.org/10.1002/advs.202004673 |
ISSN: | 2198-3844 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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