STAT1-VAMP8 axis drives nasopharyngeal carcinoma progression via autophagy enhancement

Nasopharyngeal carcinoma (NPC) is a malignant tumor with a high risk of invasion and metastasis. Elucidating the molecular underpinnings of NPC may uncover new diagnostic and therapeutic targets. Vesicle associated membrane protein 8 (VAMP8) is overexpressed and plays an oncogenic role in various tumors. However, its role and underlying mechanism in NPC remains unclear. In this study, we identified that VAMP8 is significantly overexpressed in NPC public databases (GSE150430 and GSE162025) and NPC tissues compared to adjacent tissues in NPC patients, and VAMP8 overexpression markedly accelerated tumor growth. Lysosome associated genes play major carcinogenic roles in this tumor. Further mechanistic investigations revealed that VAMP8 was involved in the development of NPC by promoting autophagy. Furthermore, we demonstrate that STAT1 transcriptionally up-regulates VAMP8, and VAMP8 overexpression rescued the tumor progression-related phenotypes mediated by STAT1 knocking down. Drug sensitive analysis based on NPC indicated that STAT1 is sensitive to fludarabine. Pharmacologically inhibiting STAT1/VAMP8 axis by fludarabine significantly suppressed the NPC cell proliferation and metastasis. Collectively, our findings establish the STAT1-VAMP8 axis as a critical driver of NPC proliferation and metastasis through autophagy activation. Fludarabine is expected to be a potential therapeutic agent in NPC patients.