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miR-200 deficiency promotes lung cancer metastasis by activating Notch signaling in cancer-associated fibroblasts
Lung adenocarcinoma, the most prevalent lung cancer subtype, is characterized by its high propensity to metastasize. Despite the importance of metastasis in lung cancer mortality, its underlying cellular and molecular mechanisms remain largely elusive. Here, we identified miR-200 miRNAs as potent su...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336896/ https://www.ncbi.nlm.nih.gov/pubmed/34301766 http://dx.doi.org/10.1101/gad.347344.120 |
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author | Xue, Bin Chuang, Chen-Hua Prosser, Haydn M. Fuziwara, Cesar Seigi Chan, Claudia Sahasrabudhe, Neil Kühn, Maximilian Wu, Yalei Chen, Jingqi Biton, Anne Chen, Caifu Wilkinson, John Erby McManus, Michael T. Bradley, Allan Winslow, Monte M. Su, Bo He, Lin |
author_facet | Xue, Bin Chuang, Chen-Hua Prosser, Haydn M. Fuziwara, Cesar Seigi Chan, Claudia Sahasrabudhe, Neil Kühn, Maximilian Wu, Yalei Chen, Jingqi Biton, Anne Chen, Caifu Wilkinson, John Erby McManus, Michael T. Bradley, Allan Winslow, Monte M. Su, Bo He, Lin |
author_sort | Xue, Bin |
collection | PubMed |
description | Lung adenocarcinoma, the most prevalent lung cancer subtype, is characterized by its high propensity to metastasize. Despite the importance of metastasis in lung cancer mortality, its underlying cellular and molecular mechanisms remain largely elusive. Here, we identified miR-200 miRNAs as potent suppressors for lung adenocarcinoma metastasis. miR-200 expression is specifically repressed in mouse metastatic lung adenocarcinomas, and miR-200 decrease strongly correlates with poor patient survival. Consistently, deletion of mir-200c/141 in the Kras(LSL-G12D/+); Trp53(flox/flox) lung adenocarcinoma mouse model significantly promoted metastasis, generating a desmoplastic tumor stroma highly reminiscent of metastatic human lung cancer. miR-200 deficiency in lung cancer cells promotes the proliferation and activation of adjacent cancer-associated fibroblasts (CAFs), which in turn elevates the metastatic potential of cancer cells. miR-200 regulates the functional interaction between cancer cells and CAFs, at least in part, by targeting Notch ligand Jagged1 and Jagged2 in cancer cells and inducing Notch activation in adjacent CAFs. Hence, the interaction between cancer cells and CAFs constitutes an essential mechanism to promote metastatic potential. |
format | Online Article Text |
id | pubmed-8336896 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-83368962022-02-01 miR-200 deficiency promotes lung cancer metastasis by activating Notch signaling in cancer-associated fibroblasts Xue, Bin Chuang, Chen-Hua Prosser, Haydn M. Fuziwara, Cesar Seigi Chan, Claudia Sahasrabudhe, Neil Kühn, Maximilian Wu, Yalei Chen, Jingqi Biton, Anne Chen, Caifu Wilkinson, John Erby McManus, Michael T. Bradley, Allan Winslow, Monte M. Su, Bo He, Lin Genes Dev Research Paper Lung adenocarcinoma, the most prevalent lung cancer subtype, is characterized by its high propensity to metastasize. Despite the importance of metastasis in lung cancer mortality, its underlying cellular and molecular mechanisms remain largely elusive. Here, we identified miR-200 miRNAs as potent suppressors for lung adenocarcinoma metastasis. miR-200 expression is specifically repressed in mouse metastatic lung adenocarcinomas, and miR-200 decrease strongly correlates with poor patient survival. Consistently, deletion of mir-200c/141 in the Kras(LSL-G12D/+); Trp53(flox/flox) lung adenocarcinoma mouse model significantly promoted metastasis, generating a desmoplastic tumor stroma highly reminiscent of metastatic human lung cancer. miR-200 deficiency in lung cancer cells promotes the proliferation and activation of adjacent cancer-associated fibroblasts (CAFs), which in turn elevates the metastatic potential of cancer cells. miR-200 regulates the functional interaction between cancer cells and CAFs, at least in part, by targeting Notch ligand Jagged1 and Jagged2 in cancer cells and inducing Notch activation in adjacent CAFs. Hence, the interaction between cancer cells and CAFs constitutes an essential mechanism to promote metastatic potential. Cold Spring Harbor Laboratory Press 2021-08-01 /pmc/articles/PMC8336896/ /pubmed/34301766 http://dx.doi.org/10.1101/gad.347344.120 Text en © 2021 Xue et al.; Published by Cold Spring Harbor Laboratory Press https://creativecommons.org/licenses/by-nc/4.0/This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Research Paper Xue, Bin Chuang, Chen-Hua Prosser, Haydn M. Fuziwara, Cesar Seigi Chan, Claudia Sahasrabudhe, Neil Kühn, Maximilian Wu, Yalei Chen, Jingqi Biton, Anne Chen, Caifu Wilkinson, John Erby McManus, Michael T. Bradley, Allan Winslow, Monte M. Su, Bo He, Lin miR-200 deficiency promotes lung cancer metastasis by activating Notch signaling in cancer-associated fibroblasts |
title | miR-200 deficiency promotes lung cancer metastasis by activating Notch signaling in cancer-associated fibroblasts |
title_full | miR-200 deficiency promotes lung cancer metastasis by activating Notch signaling in cancer-associated fibroblasts |
title_fullStr | miR-200 deficiency promotes lung cancer metastasis by activating Notch signaling in cancer-associated fibroblasts |
title_full_unstemmed | miR-200 deficiency promotes lung cancer metastasis by activating Notch signaling in cancer-associated fibroblasts |
title_short | miR-200 deficiency promotes lung cancer metastasis by activating Notch signaling in cancer-associated fibroblasts |
title_sort | mir-200 deficiency promotes lung cancer metastasis by activating notch signaling in cancer-associated fibroblasts |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8336896/ https://www.ncbi.nlm.nih.gov/pubmed/34301766 http://dx.doi.org/10.1101/gad.347344.120 |
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