Department of Radiation and Medical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang, P.R. China.
Department of Radiation Oncology, Xiang'an Hospital of Xiamen University, Fujian, P.R. China.
Oncol Res. 2019 Jul 12;27(7):801-807. doi: 10.3727/096504018X15446984186056. Epub 2019 Apr 12.
Nasopharyngeal cancer (NPC) is a malignant epithelial carcinoma of the head and neck. Cancer therapy targeting programmed cell death protein-1 (PD-1) or programmed death ligand-1 (PD-L1) is revolutionary. However, the tumorigenic mechanism of PD-L1 is not yet clear in NPC. Here we demonstrated an oncogenic role of PD-L1 via activating PI3K/AKT in NPC cells. PD-L1 overexpression was frequently detected in NPC biopsies and cell lines by qRT-PCR. PD-L1 overexpression and knockdown demonstrated that PD-L1 promoted NPC cell invasion and metastasis in vitro and in vivo. Mechanistically, PD-L1 prominently activated the epithelial-mesenchymal transition (EMT) process in a PI3K/AKT-dependent manner. Taken together, we found that PD-L1 overexpression confers NPC cell malignancy and aggressiveness via activating the downstream PI3K/AKT signaling. Thus, these results provide a basis for diagnosis and treatment of NPC.
鼻咽癌（NPC）是头颈部的一种恶性上皮癌。针对程序性细胞死亡蛋白-1（PD-1）或程序性死亡配体-1（PD-L1）的癌症治疗具有革命性意义。然而，PD-L1 在 NPC 中的致癌机制尚不清楚。在这里，我们通过在 NPC 细胞中激活 PI3K/AKT 来证明 PD-L1 的致癌作用。qRT-PCR 检测到 NPC 活检和细胞系中 PD-L1 过表达频繁。PD-L1 过表达和敲低证明 PD-L1 促进 NPC 细胞体外和体内侵袭和转移。在机制上，PD-L1 以 PI3K/AKT 依赖性方式显著激活上皮-间充质转化（EMT）过程。总之，我们发现 PD-L1 过表达通过激活下游的 PI3K/AKT 信号赋予 NPC 细胞恶性和侵袭性。因此，这些结果为 NPC 的诊断和治疗提供了依据。
