Chen Xiaochuan, Weng Youliang, Li Ying, Fu Wankai, Huang Zongwei, Pan Yuhui, Hong Wenquan, Lin Wanzun, Lin Xiandong, Qiu Sufang
Department of Radiation Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou 350000, China.
Department of Radiation Oncology, Shanghai Proton and Heavy Ion Center, Fudan University Cancer Hospital, Shanghai 201321, China.
J Oncol. 2022 Apr 30;2022:8541582. doi: 10.1155/2022/8541582. eCollection 2022.
Distant metastasis is the major cause of treatment failure in patients with nasopharyngeal carcinoma (NPC). Thus, the identification of the molecular mechanisms and the development of novel therapeutic strategies are important. Previous studies suggest that PNCK promotes tumor growth by suppressing PI3K/AKT/mTOR signaling in NPC. However, the underlying regulatory mechanism of PNCK for NPC invasion and metastasis remains unclear.
The PNCK expression level was evaluated in nonmetastatic and metastatic NPC specimens by mRNA sequencing and immunohistochemistry. In vitro migration and invasion and in vivo nude mouse metastasis model and zebrafish model were used to evaluate the effects of PNCK ectopic expression on the metastatic ability of NPC cells. Gene set enrichment and western blot analyses were used to investigate the PNCK downstream signaling pathway.
Human metastatic NPC samples showed elevated PNCK expression at both mRNA and protein levels. Upregulated PNCK promoted in vitro NPC cell migration, invasion, and the formation of lung metastases; the vascular-labeled fluorescence signal increased in the in vivo zebrafish model. Mechanistically, pathway analysis showed that the upregulation of PNCK may promote cell metastasis by activating the NF-B/VEGF signaling pathway.
These findings revealed the specific critical role of PNCK in promoting NPC metastasis and angiogenesis, which suggested that PNCK may have implications as a potential therapeutic target for individualized NPC treatment.
远处转移是鼻咽癌（NPC）患者治疗失败的主要原因。因此，确定分子机制并开发新的治疗策略很重要。先前的研究表明，PNCK通过抑制NPC中的PI3K/AKT/mTOR信号通路促进肿瘤生长。然而，PNCK对NPC侵袭和转移的潜在调控机制仍不清楚。
通过mRNA测序和免疫组织化学评估非转移性和转移性NPC标本中PNCK的表达水平。利用体外迁移和侵袭实验、体内裸鼠转移模型和斑马鱼模型评估PNCK异位表达对NPC细胞转移能力的影响。采用基因集富集分析和蛋白质印迹分析来研究PNCK下游信号通路。
人转移性NPC样本在mRNA和蛋白质水平上均显示PNCK表达升高。PNCK上调促进了体外NPC细胞的迁移、侵袭以及肺转移的形成；在体内斑马鱼模型中，血管标记的荧光信号增加。从机制上讲，通路分析表明PNCK的上调可能通过激活NF-κB/VEGF信号通路促进细胞转移。
这些发现揭示了PNCK在促进NPC转移和血管生成中的特定关键作用，这表明PNCK可能作为NPC个体化治疗的潜在靶点具有重要意义。
