Targeting ubiquitin protein ligase E3 component N-recognin 5 in cancer cells induces a CD8+ T cell mediated immune response Journal Article
| Authors: | Song, M.; Wang, C.; Wang, H.; Zhang, T.; Li, J.; Benezra, R.; Chouchane, L.; Sun, Y. H.; Cui, X. G.; Ma, X. |
| Article Title: | Targeting ubiquitin protein ligase E3 component N-recognin 5 in cancer cells induces a CD8+ T cell mediated immune response |
| Abstract: | UBR5 is a nuclear phosphoprotein of obscure functions. Clinical analyses reveal that UBR5 amplifications and overexpression occur in over 20% cases of human breast cancers. Breast cancer patients carrying UBR5 genetic lesions with overexpression have significantly reduced survival. Experimental work in vitro and in vivo demonstrates that UBR5, functioning as an oncoprotein, plays a profound role in breast cancer growth and metastasis. UBR5 drives tumor growth largely through paracrine interactions with the immune system, particularly through inhibiting the cytotoxic response mediated by CD8+ T lymphocytes, whereas it facilitates metastasis in a tumor cell-autonomous manner via its transcriptional control of key regulators of the epithelial–mesenchymal transition, ID1 and ID3. Furthermore, simultaneous targeting of UBR5 and PD-L1 yields strong therapeutic benefit to tumor-bearing hosts. This work significantly expands our scarce understanding of the pathophysiology and immunobiology of a fundamentally important molecule and has strong implications for the development of novel immunotherapy to treat highly aggressive breast cancers that resist conventional treatment. © 2020, © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC. |
| Keywords: | immunohistochemistry; signal transduction; controlled study; human tissue; protein expression; unclassified drug; cancer growth; nonhuman; flow cytometry; cd8+ t lymphocyte; animal cell; mouse; animal tissue; gene overexpression; metastasis; breast cancer; gene expression; tumor volume; animal experiment; animal model; histology; cellular immunity; immune response; genetic transfection; immunotherapy; microarray analysis; chromatin immunoprecipitation; cancer cell; western blotting; down regulation; real time polymerase chain reaction; upregulation; tumor growth; ubiquitin protein ligase e3; bioinformatics; clonogenic assay; e3 ligase; tumor microenvironment; rna analysis; rna isolation; liquid chromatography-mass spectrometry; human; article; cell proliferation assay; ubr5; ubiquitin protein ligase e3 component n recognin 5; transwell assay |
| Journal Title: | OncoImmunology |
| Volume: | 9 |
| Issue: | 1 |
| ISSN: | 2162-4011 |
| Publisher: | Landes Bioscience |
| Date Published: | 2020-01-01 |
| Start Page: | e1746148 |
| Language: | English |
| DOI: | 10.1080/2162402x.2020.1746148 |
| PROVIDER: | scopus |
| PMCID: | PMC7185213 |
| PUBMED: | 32363114 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 May 2020 -- Source: Scopus |
