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Phase separation of DDX21 promotes colorectal cancer metastasis via MCM5-dependent EMT pathway

RNA binding proteins (RBPs) contributes to cancer progression, but the underlying mechanism reminds unclear. Here, we find that DDX21, a representative RBP, is highly expressed in colorectal cancer (CRC), which leads to CRC cell migration and invasion in vitro, and CRC to liver metastasis and lung m...

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Autores principales: Gao, Huabin, Wei, Huiting, Yang, Yang, Li, Hui, Liang, Jiangtao, Ye, Jiecheng, Zhang, Fenfen, Wang, Liyuan, Shi, Huijuan, Wang, Jia, Han, Anjia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10202810/
https://www.ncbi.nlm.nih.gov/pubmed/37029300
http://dx.doi.org/10.1038/s41388-023-02687-6
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author Gao, Huabin
Wei, Huiting
Yang, Yang
Li, Hui
Liang, Jiangtao
Ye, Jiecheng
Zhang, Fenfen
Wang, Liyuan
Shi, Huijuan
Wang, Jia
Han, Anjia
author_facet Gao, Huabin
Wei, Huiting
Yang, Yang
Li, Hui
Liang, Jiangtao
Ye, Jiecheng
Zhang, Fenfen
Wang, Liyuan
Shi, Huijuan
Wang, Jia
Han, Anjia
author_sort Gao, Huabin
collection PubMed
description RNA binding proteins (RBPs) contributes to cancer progression, but the underlying mechanism reminds unclear. Here, we find that DDX21, a representative RBP, is highly expressed in colorectal cancer (CRC), which leads to CRC cell migration and invasion in vitro, and CRC to liver metastasis and lung metastasis in vivo. This effect of DDX21 on CRC metastasis is correlated to the activation of Epithelial-mesenchymal transition (EMT) pathway. Moreover, we reveal that DDX21 protein is phase separated in vitro and in CRC cells, which controls CRC metastasis. Phase-separated DDX21 highly binds on MCM5 gene locus, which is markedly reduced when phase separation is disrupted by mutations on its intrinsically disordered region (IDR). The impaired metastatic ability of CRC upon DDX21 loss is restored by ectopic expression of MCM5, indicating MCM5 is a key downstream target of DDX21 for CRC metastasis. Furthermore, co-higher expressions of DDX21 and MCM5 is significantly correlated with poor survival outcomes of stage III and IV CRC patients, indicating the importance of this mechanism in CRC late and metastatic stage. Altogether, our results elucidate a new model of DDX21 in regulating CRC metastasis via phase separation.
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spelling pubmed-102028102023-05-24 Phase separation of DDX21 promotes colorectal cancer metastasis via MCM5-dependent EMT pathway Gao, Huabin Wei, Huiting Yang, Yang Li, Hui Liang, Jiangtao Ye, Jiecheng Zhang, Fenfen Wang, Liyuan Shi, Huijuan Wang, Jia Han, Anjia Oncogene Article RNA binding proteins (RBPs) contributes to cancer progression, but the underlying mechanism reminds unclear. Here, we find that DDX21, a representative RBP, is highly expressed in colorectal cancer (CRC), which leads to CRC cell migration and invasion in vitro, and CRC to liver metastasis and lung metastasis in vivo. This effect of DDX21 on CRC metastasis is correlated to the activation of Epithelial-mesenchymal transition (EMT) pathway. Moreover, we reveal that DDX21 protein is phase separated in vitro and in CRC cells, which controls CRC metastasis. Phase-separated DDX21 highly binds on MCM5 gene locus, which is markedly reduced when phase separation is disrupted by mutations on its intrinsically disordered region (IDR). The impaired metastatic ability of CRC upon DDX21 loss is restored by ectopic expression of MCM5, indicating MCM5 is a key downstream target of DDX21 for CRC metastasis. Furthermore, co-higher expressions of DDX21 and MCM5 is significantly correlated with poor survival outcomes of stage III and IV CRC patients, indicating the importance of this mechanism in CRC late and metastatic stage. Altogether, our results elucidate a new model of DDX21 in regulating CRC metastasis via phase separation. Nature Publishing Group UK 2023-04-07 2023 /pmc/articles/PMC10202810/ /pubmed/37029300 http://dx.doi.org/10.1038/s41388-023-02687-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Gao, Huabin
Wei, Huiting
Yang, Yang
Li, Hui
Liang, Jiangtao
Ye, Jiecheng
Zhang, Fenfen
Wang, Liyuan
Shi, Huijuan
Wang, Jia
Han, Anjia
Phase separation of DDX21 promotes colorectal cancer metastasis via MCM5-dependent EMT pathway
title Phase separation of DDX21 promotes colorectal cancer metastasis via MCM5-dependent EMT pathway
title_full Phase separation of DDX21 promotes colorectal cancer metastasis via MCM5-dependent EMT pathway
title_fullStr Phase separation of DDX21 promotes colorectal cancer metastasis via MCM5-dependent EMT pathway
title_full_unstemmed Phase separation of DDX21 promotes colorectal cancer metastasis via MCM5-dependent EMT pathway
title_short Phase separation of DDX21 promotes colorectal cancer metastasis via MCM5-dependent EMT pathway
title_sort phase separation of ddx21 promotes colorectal cancer metastasis via mcm5-dependent emt pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10202810/
https://www.ncbi.nlm.nih.gov/pubmed/37029300
http://dx.doi.org/10.1038/s41388-023-02687-6
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