Deubiquitination and stabilization of programmed cell death ligand 1 by ubiquitin-specific peptidase 9, X-linked in oral squamous cell carcinoma.
Deubiquitination and stabilization of programmed cell death ligand 1 by ubiquitin-specific peptidase 9, X-linked in oral squamous cell carcinoma.
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口腔鳞状细胞癌中X连锁泛素特异性肽酶9对程序性细胞死亡配体1的去泛素化和稳定化
DOI：
10.1002/cam4.1675
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发表时间：
2018-08
期刊：
影响因子：
4
通讯作者：
Wenjuan W
中科院分区：
文献类型：
--
作者：
Jingjing W;Wenzheng G;Donghua W;Guangyu H;Aiping Z;Wenjuan W
免疫检查点蛋白程序性细胞死亡配体1（PD-L1）与PD 1结合，促进肿瘤细胞逃避免疫系统的杀伤作用。然而，关于PD-L1在肿瘤中的调节机制的研究很少。虽然PD-L1已被报道在某些癌症中发生泛素化，但其在口腔鳞状细胞癌（OSCC）中的调控机制尚不清楚。因此，我们的目的是调查这一现象。我们使用蛋白质印迹法、免疫沉淀法、免疫组织化学（IHC）、T细胞介导的肿瘤细胞杀伤试验和液相色谱-质谱法检测了USP 9 X和PD-L1在人口腔角质形成细胞（HOK）和OSCC细胞系（HN 4和HN 30）（作为对照和相关癌细胞）中的表达和功能。程序性细胞死亡配体1通过泛素-蛋白酶体途径在口腔鳞癌中高表达。此外，我们发现泛素特异性肽酶9，X-连锁（USP 9 X）可以与PD-L1结合，以诱导其去泛素化并稳定其在OSCC中的蛋白表达。我们的数据表明，USP 9 X去泛素化和稳定PD-L1。抑制USP 9 X的表达可阻断肿瘤细胞生长。该结果为USP 9 X作为治疗靶点提供了理论依据。
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. 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. 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. 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.
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影响因子：
4
作者：
Matsukawa, Sho;Morita, Kei-ichi;Negishi, Ayako;Harada, Hiroyuki;Nakajima, Yusuke;Shimamoto, Hiroaki;Tomioka, Hirofumi;Tanaka, Kae;Ono, Masaya;Yamada, Tesshi;Omura, Ken
通讯作者：
Omura, Ken
影响因子：
16.6
作者：
Potu H;Peterson LF;Kandarpa M;Pal A;Sun H;Durham A;Harms PW;Hollenhorst PC;Eskiocak U;Talpaz M;Donato NJ
通讯作者：
Donato NJ
影响因子：
5.2
作者：
Hirai M;Kitahara H;Kobayashi Y;Kato K;Bou-Gharios G;Nakamura H;Kawashiri S
通讯作者：
Kawashiri S
影响因子：
3.7
作者：
Huang G;Wen Q;Zhao Y;Gao Q;Bai Y
通讯作者：
Bai Y
影响因子：
4.8
作者：
Fakhry, Carole;D'Souza, Gypsyamber
通讯作者：
D'Souza, Gypsyamber