Tumor derived UBR5 promotes ovarian cancer growth and metastasis through inducing immunosuppressive macrophages Journal Article
| Authors: | Song, M.; Yeku, O. O.; Rafiq, S.; Purdon, T.; Dong, X.; Zhu, L.; Zhang, T.; Wang, H.; Yu, Z.; Mai, J.; Shen, H.; Nixon, B.; Li, M.; Brentjens, R. J.; Ma, X. |
| Article Title: | Tumor derived UBR5 promotes ovarian cancer growth and metastasis through inducing immunosuppressive macrophages |
| Abstract: | 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. © 2020, The Author(s). |
| Keywords: | survival; chemotherapy; gene expression; protein; tumor; growth rate; cancer |
| Journal Title: | Nature Communications |
| Volume: | 11 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2020-12-08 |
| Start Page: | 6298 |
| Language: | English |
| DOI: | 10.1038/s41467-020-20140-0 |
| PUBMED: | 33293516 |
| PROVIDER: | scopus |
| PMCID: | PMC7722725 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 4 January 2021 -- Source: Scopus |
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