Upregulation of PNCK Promotes Metastasis and Angiogenesis via Activating NF-κB/VEGF Pathway in Nasopharyngeal Carcinoma

Autor: Xiaochuan Chen, Youliang Weng, Ying Li, Wankai Fu, Zongwei Huang, Yuhui Pan, Wenquan Hong, Wanzun Lin, Xiandong Lin, Sufang Qiu
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Journal of Oncology.
ISSN: 1687-8450
DOI: 10.1155/2022/8541582
Popis: Background. 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. Methods. 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. Results. 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-κB/VEGF signaling pathway. Conclusions. 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.
Databáze: OpenAIRE
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