Cargando…
Deubiquitination and stabilization of programmed cell death ligand 1 by ubiquitin‐specific peptidase 9, X‐linked in oral squamous cell carcinoma
BACKGROUND: The immune checkpoint protein programmed cell death ligand 1 (PD‐L1) binds to PD1 to promote tumor cell escape from the killing effect of the immune system. However, there are few studies on the regulatory mechanisms of PD‐L1 in tumors. Although PD‐L1 has been reported to undergo ubiquit...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6089178/ https://www.ncbi.nlm.nih.gov/pubmed/29992764 http://dx.doi.org/10.1002/cam4.1675 |
_version_ | 1783346980802527232 |
---|---|
author | Jingjing, Wu Wenzheng, Guo Donghua, Wen Guangyu, Hou Aiping, Zhou Wenjuan, Wu |
author_facet | Jingjing, Wu Wenzheng, Guo Donghua, Wen Guangyu, Hou Aiping, Zhou Wenjuan, Wu |
author_sort | Jingjing, Wu |
collection | PubMed |
description | BACKGROUND: The immune checkpoint protein programmed cell death ligand 1 (PD‐L1) binds to PD1 to promote tumor cell escape from the killing effect of the immune system. However, there are few studies on the regulatory mechanisms of PD‐L1 in tumors. Although PD‐L1 has been reported to undergo ubiquitination in some cancers, its regulatory mechanisms in oral squamous cell carcinoma (OSCC) are unclear. Therefore, we aimed to investigate this phenomenon. METHODS: We examined the expression and function of USP9X and PD‐L1 in human oral keratinocytes (HOK) and OSCC cell lines (HN4 and HN30) as the control and relevant cancer cells using western blotting, immunoprecipitation, immunohistochemistry (IHC), T‐cell‐mediated tumor cell killing assay, and liquid chromatography‐mass spectrometry. RESULTS: Programmed cell death ligand 1 was highly expressed in OSCC by the regulation of the ubiquitin‐proteasome pathway. Furthermore, we discovered that ubiquitin‐specific peptidase 9, X‐linked (USP9X) could be combined with PD‐L1 to induce its deubiquitination and stabilize its protein expression in OSCC. CONCLUSION: Our data indicate that USP9X deubiquitinates and stabilizes PD‐L1. Suppressing the expression of USP9X blocks tumor cell growth. The results provide a theoretical basis for USP9X as a therapeutic target. |
format | Online Article Text |
id | pubmed-6089178 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-60891782018-08-17 Deubiquitination and stabilization of programmed cell death ligand 1 by ubiquitin‐specific peptidase 9, X‐linked in oral squamous cell carcinoma Jingjing, Wu Wenzheng, Guo Donghua, Wen Guangyu, Hou Aiping, Zhou Wenjuan, Wu Cancer Med Cancer Biology BACKGROUND: The immune checkpoint protein programmed cell death ligand 1 (PD‐L1) binds to PD1 to promote tumor cell escape from the killing effect of the immune system. However, there are few studies on the regulatory mechanisms of PD‐L1 in tumors. Although PD‐L1 has been reported to undergo ubiquitination in some cancers, its regulatory mechanisms in oral squamous cell carcinoma (OSCC) are unclear. Therefore, we aimed to investigate this phenomenon. METHODS: We examined the expression and function of USP9X and PD‐L1 in human oral keratinocytes (HOK) and OSCC cell lines (HN4 and HN30) as the control and relevant cancer cells using western blotting, immunoprecipitation, immunohistochemistry (IHC), T‐cell‐mediated tumor cell killing assay, and liquid chromatography‐mass spectrometry. RESULTS: Programmed cell death ligand 1 was highly expressed in OSCC by the regulation of the ubiquitin‐proteasome pathway. Furthermore, we discovered that ubiquitin‐specific peptidase 9, X‐linked (USP9X) could be combined with PD‐L1 to induce its deubiquitination and stabilize its protein expression in OSCC. CONCLUSION: Our data indicate that USP9X deubiquitinates and stabilizes PD‐L1. Suppressing the expression of USP9X blocks tumor cell growth. The results provide a theoretical basis for USP9X as a therapeutic target. John Wiley and Sons Inc. 2018-07-10 /pmc/articles/PMC6089178/ /pubmed/29992764 http://dx.doi.org/10.1002/cam4.1675 Text en © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Cancer Biology Jingjing, Wu Wenzheng, Guo Donghua, Wen Guangyu, Hou Aiping, Zhou Wenjuan, Wu Deubiquitination and stabilization of programmed cell death ligand 1 by ubiquitin‐specific peptidase 9, X‐linked in oral squamous cell carcinoma |
title | Deubiquitination and stabilization of programmed cell death ligand 1 by ubiquitin‐specific peptidase 9, X‐linked in oral squamous cell carcinoma |
title_full | Deubiquitination and stabilization of programmed cell death ligand 1 by ubiquitin‐specific peptidase 9, X‐linked in oral squamous cell carcinoma |
title_fullStr | Deubiquitination and stabilization of programmed cell death ligand 1 by ubiquitin‐specific peptidase 9, X‐linked in oral squamous cell carcinoma |
title_full_unstemmed | Deubiquitination and stabilization of programmed cell death ligand 1 by ubiquitin‐specific peptidase 9, X‐linked in oral squamous cell carcinoma |
title_short | Deubiquitination and stabilization of programmed cell death ligand 1 by ubiquitin‐specific peptidase 9, X‐linked in oral squamous cell carcinoma |
title_sort | deubiquitination and stabilization of programmed cell death ligand 1 by ubiquitin‐specific peptidase 9, x‐linked in oral squamous cell carcinoma |
topic | Cancer Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6089178/ https://www.ncbi.nlm.nih.gov/pubmed/29992764 http://dx.doi.org/10.1002/cam4.1675 |
work_keys_str_mv | AT jingjingwu deubiquitinationandstabilizationofprogrammedcelldeathligand1byubiquitinspecificpeptidase9xlinkedinoralsquamouscellcarcinoma AT wenzhengguo deubiquitinationandstabilizationofprogrammedcelldeathligand1byubiquitinspecificpeptidase9xlinkedinoralsquamouscellcarcinoma AT donghuawen deubiquitinationandstabilizationofprogrammedcelldeathligand1byubiquitinspecificpeptidase9xlinkedinoralsquamouscellcarcinoma AT guangyuhou deubiquitinationandstabilizationofprogrammedcelldeathligand1byubiquitinspecificpeptidase9xlinkedinoralsquamouscellcarcinoma AT aipingzhou deubiquitinationandstabilizationofprogrammedcelldeathligand1byubiquitinspecificpeptidase9xlinkedinoralsquamouscellcarcinoma AT wenjuanwu deubiquitinationandstabilizationofprogrammedcelldeathligand1byubiquitinspecificpeptidase9xlinkedinoralsquamouscellcarcinoma |