USP5 facilitates non-small cell lung cancer progression through stabilization of PD-L1.
Cell Death Dis
; 12(11): 1051, 2021 11 05.
Article
in En
| MEDLINE
| ID: mdl-34741014
ABSTRACT
PD-L1(CD274) is a well-known immunosuppressive molecule, which confers immunoescape features to cancer cells and has become one of the major targets in cancer immunotherapies. Understanding the regulatory mechanisms that control PD-L1 protein expression is important for guiding immune checkpoint blockade therapy. Here, we showed that ubiquitin specific peptidase 5 (USP5) was a novel PD-L1 deubiquitinase in non-small cell lung cancer (NSCLC) cells. USP5 directly interacted with PD-L1 and deubiquitinated PD-L1, therefore enhances PD-L1 protein stability. Meanwhile, USP5 protein levels were highly elevated and positively correlated to PD-L1 levels in NSCLC tissues, and were closely correlated with poor prognosis of these patients. In addition, knockdown of USP5 retarded tumor growth in the Lewis lung carcinoma mouse model. Thus, we identified that USP5 was a new regulator of PD-L1 and targeting USP5 is a promising strategy for cancer therapy.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Endopeptidases
/
Carcinoma, Non-Small-Cell Lung
/
Disease Progression
/
B7-H1 Antigen
/
Lung Neoplasms
Type of study:
Prognostic_studies
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
En
Journal:
Cell Death Dis
Year:
2021
Document type:
Article