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Tumor derived UBR5 promotes ovarian cancer growth and metastasis through inducing immunosuppressive macrophages
Immunosuppressive tumor microenvironment (TME) and ascites-derived spheroids in ovarian cancer (OC) facilitate tumor growth and progression, and also pose major obstacles for cancer therapy. The molecular pathways involved in the OC-TME interactions, how the crosstalk impinges on OC aggression and c...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722725/ https://www.ncbi.nlm.nih.gov/pubmed/33293516 http://dx.doi.org/10.1038/s41467-020-20140-0 |
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author | Song, Mei Yeku, Oladapo O. Rafiq, Sarwish Purdon, Terence Dong, Xue Zhu, Lijing Zhang, Tuo Wang, Huan Yu, Ziqi Mai, Junhua Shen, Haifa Nixon, Briana Li, Ming Brentjens, Renier J. Ma, Xiaojing |
author_facet | Song, Mei Yeku, Oladapo O. Rafiq, Sarwish Purdon, Terence Dong, Xue Zhu, Lijing Zhang, Tuo Wang, Huan Yu, Ziqi Mai, Junhua Shen, Haifa Nixon, Briana Li, Ming Brentjens, Renier J. Ma, Xiaojing |
author_sort | Song, Mei |
collection | PubMed |
description | Immunosuppressive tumor microenvironment (TME) and ascites-derived spheroids in ovarian cancer (OC) facilitate tumor growth and progression, and also pose major obstacles for cancer therapy. The molecular pathways involved in the OC-TME interactions, how the crosstalk impinges on OC aggression and chemoresistance are not well-characterized. Here, we demonstrate that tumor-derived UBR5, an E3 ligase overexpressed in human OC associated with poor prognosis, is essential for OC progression principally by promoting tumor-associated macrophage recruitment and activation via key chemokines and cytokines. UBR5 is also required to sustain cell-intrinsic β-catenin-mediated signaling to promote cellular adhesion/colonization and organoid formation by controlling the p53 protein level. OC-specific targeting of UBR5 strongly augments the survival benefit of conventional chemotherapy and immunotherapies. This work provides mechanistic insights into the novel oncogene-like functions of UBR5 in regulating the OC-TME crosstalk and suggests that UBR5 is a potential therapeutic target in OC treatment for modulating the TME and cancer stemness. |
format | Online Article Text |
id | pubmed-7722725 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-77227252020-12-11 Tumor derived UBR5 promotes ovarian cancer growth and metastasis through inducing immunosuppressive macrophages Song, Mei Yeku, Oladapo O. Rafiq, Sarwish Purdon, Terence Dong, Xue Zhu, Lijing Zhang, Tuo Wang, Huan Yu, Ziqi Mai, Junhua Shen, Haifa Nixon, Briana Li, Ming Brentjens, Renier J. Ma, Xiaojing Nat Commun Article Immunosuppressive tumor microenvironment (TME) and ascites-derived spheroids in ovarian cancer (OC) facilitate tumor growth and progression, and also pose major obstacles for cancer therapy. The molecular pathways involved in the OC-TME interactions, how the crosstalk impinges on OC aggression and chemoresistance are not well-characterized. Here, we demonstrate that tumor-derived UBR5, an E3 ligase overexpressed in human OC associated with poor prognosis, is essential for OC progression principally by promoting tumor-associated macrophage recruitment and activation via key chemokines and cytokines. UBR5 is also required to sustain cell-intrinsic β-catenin-mediated signaling to promote cellular adhesion/colonization and organoid formation by controlling the p53 protein level. OC-specific targeting of UBR5 strongly augments the survival benefit of conventional chemotherapy and immunotherapies. This work provides mechanistic insights into the novel oncogene-like functions of UBR5 in regulating the OC-TME crosstalk and suggests that UBR5 is a potential therapeutic target in OC treatment for modulating the TME and cancer stemness. Nature Publishing Group UK 2020-12-08 /pmc/articles/PMC7722725/ /pubmed/33293516 http://dx.doi.org/10.1038/s41467-020-20140-0 Text en © The Author(s) 2020 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/. |
spellingShingle | Article Song, Mei Yeku, Oladapo O. Rafiq, Sarwish Purdon, Terence Dong, Xue Zhu, Lijing Zhang, Tuo Wang, Huan Yu, Ziqi Mai, Junhua Shen, Haifa Nixon, Briana Li, Ming Brentjens, Renier J. Ma, Xiaojing Tumor derived UBR5 promotes ovarian cancer growth and metastasis through inducing immunosuppressive macrophages |
title | Tumor derived UBR5 promotes ovarian cancer growth and metastasis through inducing immunosuppressive macrophages |
title_full | Tumor derived UBR5 promotes ovarian cancer growth and metastasis through inducing immunosuppressive macrophages |
title_fullStr | Tumor derived UBR5 promotes ovarian cancer growth and metastasis through inducing immunosuppressive macrophages |
title_full_unstemmed | Tumor derived UBR5 promotes ovarian cancer growth and metastasis through inducing immunosuppressive macrophages |
title_short | Tumor derived UBR5 promotes ovarian cancer growth and metastasis through inducing immunosuppressive macrophages |
title_sort | tumor derived ubr5 promotes ovarian cancer growth and metastasis through inducing immunosuppressive macrophages |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722725/ https://www.ncbi.nlm.nih.gov/pubmed/33293516 http://dx.doi.org/10.1038/s41467-020-20140-0 |
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