# AK4 promotes nasopharyngeal carcinoma metastasis and chemoresistance by activating NLRP3 inflammatory complex

## TL;DR

This study shows that the gene AK4 helps cancer spread and resist treatment in nasopharyngeal carcinoma by activating a specific inflammatory pathway.

## Contribution

AK4 is identified as a novel driver of metastasis and chemoresistance in NPC through activation of the NLRP3 inflammatory complex.

## Key findings

- AK4 is upregulated in NPC and linked to metastasis and chemoresistance.
- AK4 promotes cancer cell migration, invasion, and EMT by activating the NLRP3 pathway.
- AK4 represents a potential therapeutic target for NPC treatment.

## Abstract

Metastasis is the main cause of treatment failure in nasopharyngeal carcinoma (NPC). Our previous study developed a transcriptomics-based gene signature (AK4, CPAMD8, DDAH1, and CRTR1) to predict metastasis in NPC and identify candidates that could benefit from induction chemotherapy (IC). Of these, adenylate kinase 4 (AK4) is a potent oncogene involved in the malignant progression of a variety of tumors. This study investigated the expression and mechanism of action of AK4, a member of the AK family of enzymes, in NPC. Quantitative real-time PCR, western blotting, and immunohistochemistry revealed that AK4 was upregulated in NPC and correlated with metastasis and chemoresistance. Stable ectopic overexpression of AK4 in NPC cell lines conferred resistance to taxol-induced apoptosis, promoted the migration, invasion, and EMT phenotype, and induced IL-1β secretion by activating the NLRP3 signaling pathway; knockdown of AK4 had the opposite effects. Mechanistically, AK4 co-localized with NNT, upregulated NLRP3 and IL-1β, and consequently altered NPC cell metastasis and chemoresistance. AK4 may play a role in the development of NPC and represent a potential therapeutic target.