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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 bin...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498885/ https://www.ncbi.nlm.nih.gov/pubmed/34378358 http://dx.doi.org/10.1002/advs.202004673 |
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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, Victor Gersbach, Charles Crawford, Gregory Hsu, David Huang, Emina Bu, Pengcheng Shen, Xiling |
author_facet | 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, Victor Gersbach, Charles Crawford, Gregory Hsu, David Huang, Emina Bu, Pengcheng Shen, Xiling |
author_sort | Wang, Lihua |
collection | PubMed |
description | 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/dCas9(KRAB) or CRISPR/dCas9(HDAC) 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. |
format | Online Article Text |
id | pubmed-8498885 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84988852021-10-12 Chromatin Remodeling of Colorectal Cancer Liver Metastasis is Mediated by an HGF‐PU.1‐DPP4 Axis 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, Victor Gersbach, Charles Crawford, Gregory Hsu, David Huang, Emina Bu, Pengcheng Shen, Xiling Adv Sci (Weinh) Research Articles 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/dCas9(KRAB) or CRISPR/dCas9(HDAC) 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. John Wiley and Sons Inc. 2021-08-10 /pmc/articles/PMC8498885/ /pubmed/34378358 http://dx.doi.org/10.1002/advs.202004673 Text en © 2021 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles 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, Victor Gersbach, Charles Crawford, Gregory Hsu, David Huang, Emina Bu, Pengcheng Shen, Xiling Chromatin Remodeling of Colorectal Cancer Liver Metastasis is Mediated by an HGF‐PU.1‐DPP4 Axis |
title | Chromatin Remodeling of Colorectal Cancer Liver Metastasis is Mediated by an HGF‐PU.1‐DPP4 Axis |
title_full | Chromatin Remodeling of Colorectal Cancer Liver Metastasis is Mediated by an HGF‐PU.1‐DPP4 Axis |
title_fullStr | Chromatin Remodeling of Colorectal Cancer Liver Metastasis is Mediated by an HGF‐PU.1‐DPP4 Axis |
title_full_unstemmed | Chromatin Remodeling of Colorectal Cancer Liver Metastasis is Mediated by an HGF‐PU.1‐DPP4 Axis |
title_short | Chromatin Remodeling of Colorectal Cancer Liver Metastasis is Mediated by an HGF‐PU.1‐DPP4 Axis |
title_sort | chromatin remodeling of colorectal cancer liver metastasis is mediated by an hgf‐pu.1‐dpp4 axis |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498885/ https://www.ncbi.nlm.nih.gov/pubmed/34378358 http://dx.doi.org/10.1002/advs.202004673 |
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