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Loss of myeloid‐specific lamin A/C drives lung metastasis through Gfi‐1 and C/EBPε‐mediated granulocytic differentiation
The immune‐suppressive tumor microenvironment promotes metastatic spread and outgrowth. One of the major contributors is tumor‐associated myeloid cells. However, the molecular mechanisms regulating their differentiation and function are not well understood. Here we report lamin A/C, a nuclear lamina...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282947/ https://www.ncbi.nlm.nih.gov/pubmed/31912614 http://dx.doi.org/10.1002/mc.23147 |
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author | Ishii, Hiroki Park, Woo‐Yong So, Jaeyoung Kuhn, Skyler Koparde, Vishal N. Pang, Yanli Greten, Tim F. Hollander, M. Christine Yang, Li |
author_facet | Ishii, Hiroki Park, Woo‐Yong So, Jaeyoung Kuhn, Skyler Koparde, Vishal N. Pang, Yanli Greten, Tim F. Hollander, M. Christine Yang, Li |
author_sort | Ishii, Hiroki |
collection | PubMed |
description | The immune‐suppressive tumor microenvironment promotes metastatic spread and outgrowth. One of the major contributors is tumor‐associated myeloid cells. However, the molecular mechanisms regulating their differentiation and function are not well understood. Here we report lamin A/C, a nuclear lamina protein associated with chromatin remodeling, was one of the critical regulators in cellular reprogramming of tumor‐associated myeloid cells. Using myeloid‐specific lamin A/C knockout mice and triple‐negative breast cancer (TNBC) mouse models, we discovered that the loss of lamin A/C drives CD11b(+)Ly6G(+) granulocytic lineage differentiation, alters the production of inflammatory chemokines, decreases host antitumor immunity, and increases metastasis. The underlying mechanisms involve an increased H3K4me3 leading to the upregulation of transcription factors (TFs) Gfi‐1 and C/EBPε. Decreased lamin A/C and increased Gfi‐1 and C/EBPε were also found in the granulocytic subset in the peripheral blood of human cancer patients. Our data provide a mechanistic understanding of myeloid lineage differentiation and function in the immune‐suppressive microenvironment in TNBC metastasis. |
format | Online Article Text |
id | pubmed-7282947 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-72829472020-09-25 Loss of myeloid‐specific lamin A/C drives lung metastasis through Gfi‐1 and C/EBPε‐mediated granulocytic differentiation Ishii, Hiroki Park, Woo‐Yong So, Jaeyoung Kuhn, Skyler Koparde, Vishal N. Pang, Yanli Greten, Tim F. Hollander, M. Christine Yang, Li Mol Carcinog Research Articles The immune‐suppressive tumor microenvironment promotes metastatic spread and outgrowth. One of the major contributors is tumor‐associated myeloid cells. However, the molecular mechanisms regulating their differentiation and function are not well understood. Here we report lamin A/C, a nuclear lamina protein associated with chromatin remodeling, was one of the critical regulators in cellular reprogramming of tumor‐associated myeloid cells. Using myeloid‐specific lamin A/C knockout mice and triple‐negative breast cancer (TNBC) mouse models, we discovered that the loss of lamin A/C drives CD11b(+)Ly6G(+) granulocytic lineage differentiation, alters the production of inflammatory chemokines, decreases host antitumor immunity, and increases metastasis. The underlying mechanisms involve an increased H3K4me3 leading to the upregulation of transcription factors (TFs) Gfi‐1 and C/EBPε. Decreased lamin A/C and increased Gfi‐1 and C/EBPε were also found in the granulocytic subset in the peripheral blood of human cancer patients. Our data provide a mechanistic understanding of myeloid lineage differentiation and function in the immune‐suppressive microenvironment in TNBC metastasis. John Wiley and Sons Inc. 2020-01-07 2020-07 /pmc/articles/PMC7282947/ /pubmed/31912614 http://dx.doi.org/10.1002/mc.23147 Text en © 2020 The Authors. Molecular Carcinogenesis Published by Wiley Periodicals LLC This is an open access article under the terms of the http://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 Ishii, Hiroki Park, Woo‐Yong So, Jaeyoung Kuhn, Skyler Koparde, Vishal N. Pang, Yanli Greten, Tim F. Hollander, M. Christine Yang, Li Loss of myeloid‐specific lamin A/C drives lung metastasis through Gfi‐1 and C/EBPε‐mediated granulocytic differentiation |
title | Loss of myeloid‐specific lamin A/C drives lung metastasis through Gfi‐1 and C/EBPε‐mediated granulocytic differentiation |
title_full | Loss of myeloid‐specific lamin A/C drives lung metastasis through Gfi‐1 and C/EBPε‐mediated granulocytic differentiation |
title_fullStr | Loss of myeloid‐specific lamin A/C drives lung metastasis through Gfi‐1 and C/EBPε‐mediated granulocytic differentiation |
title_full_unstemmed | Loss of myeloid‐specific lamin A/C drives lung metastasis through Gfi‐1 and C/EBPε‐mediated granulocytic differentiation |
title_short | Loss of myeloid‐specific lamin A/C drives lung metastasis through Gfi‐1 and C/EBPε‐mediated granulocytic differentiation |
title_sort | loss of myeloid‐specific lamin a/c drives lung metastasis through gfi‐1 and c/ebpε‐mediated granulocytic differentiation |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282947/ https://www.ncbi.nlm.nih.gov/pubmed/31912614 http://dx.doi.org/10.1002/mc.23147 |
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