Serum Starvation-induced ROS Production Activates the ERK-AP-1-TfR1 Pathway to Up-regulate Survivin to Support Nasopharyngeal Carcinoma Cell Viability.

BACKGROUND/AIM: Transferrin receptor 1 (TfR1), a cell surface protein involved in iron transport, has been detected in nasopharyngeal carcinoma (NPC) biopsies and is associated with NPC malignancy. However, the mechanisms regulating TfR1 expression in NPC are not well understood. This study aimed to investigate whether and how serum starvation, a nutrient-deficient model often associated with tumor development, affects TfR1 expression in NPC cells.

MATERIALS AND METHODS

Two NPC cell lines, NPC-TW01 and NPC/HK1, were used for this study. Various assays, including MTT, reactive oxygen species (ROS) detection, luciferase reporter, and immunoblotting, were conducted to assess cell viability, ROS production, AP-1 activity, and protein expression, respectively.

RESULTS

Serum starvation significantly increased both TfR1 mRNA and protein expression in NPC cells. Activation of the ERK-AP-1 pathway is essential for TfR1 expression during serum starvation. Additionally, serum starvation induced ROS production, which is required for ERK activation. Knockdown of TfR1 using specific siRNAs resulted in decreased survivin expression, and treatment with YM155, a survivin inhibitor, significantly reduced the viability of serum-starved NPC cells.

CONCLUSION

The serum starvation-induced ROS-ERK-AP-1 axis is crucial for the up-regulation of TfR1, which contributes to survivin expression and ultimately sustains the viability of NPC cells.