Wang, LihuaWang, ErgangPrado Balcazar, JorgeWu, ZhenzhenXiang, KunWang, YiHuang, QiangNegrete, MarcosChen, Kai‐yuanLi, WeiFu, YujieDohlman, AndersMines, RobertZhang, LiwenKobayashi, YoshihikoChen, TianyiShi, GuizhiShen, John PaulKopetz, ScottTata, Purushothama RaoMoreno Aguado, VíctorGersbach, CharlesCrawford, GregoryHsu, DavidHuang, EminaBu, PengchengShen, Xiling2021-09-102021-09-102021-08-102198-3844https://hdl.handle.net/2445/179937Colorectal 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.15 p.application/pdfengcc by (c) Wang, Lihua et al, 2021http://creativecommons.org/licenses/by/3.0/es/Càncer colorectalMetàstasiColorectal cancerMetastasisinfo:eu-repo/semantics/article2021-09-10info:eu-repo/semantics/openAccess34378358