Affiliation:
1. Guangdong University of Technology
2. Guangdong Medical University
3. Sun Yat-sen University Cancer Center
Abstract
Abstract
Background
Nasopharyngeal carcinoma (NPC) is a malignant tumor with a high risk of local invasion and early distant metastasis. Resistin is an inflammatory cytokine predominantly produced from the immunocytes in humans. Accumulating evidence suggested clinical association of circulating resistin with the risk of tumorigenesis, the relationship between blood resistin levels and the risk of cancer metastasis. In this study, we explored the blood levels and the role of resistin in NPC.
Methods
A hospital-based case control study was used to assess the association of circulating resistin level with the risk of NPC and clinicopathological characteristics. Wound-healing and Transwell assays were applied to confirm the effects of resistin on NPC cell invasion and migration. A mouse model for lung metastasis was used to explore the role of resistin in NPC tumor metastasis. We also investigated the underlying signaling mechanisms with various specific pharmacological inhibitors and biochemistry analysis.
Results
High resistin levels in NPC patients positively association with lymph node metastasis, and resistin promoted the migration and invasion of NPC cells in vitro. These findings were also replicated in the mouse model of NPC tumor metastasis. We further showed that activation of p38 MAPK pathway was critical for resistin-induced migration and invasion through interaction with TLR4 with NF-κB as the primary mediator of resistin induced epithelial-mesenchymal transition in NPC cells.
Conclusion
Taken together, our results suggests that resistin promotes NPC metastasis through activating the TLR4/p38 MAPK/NF-κB signaling pathway.
Publisher
Research Square Platform LLC
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