Serum Starvation-induced ROS Production Activates the ERK-AP-1-TfR1 Pathway to Up-regulate Survivin to Support Nasopharyngeal Carcinoma Cell Viability
Year: 2025
Type: article
Abstract: 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.
Source: Cancer Genomics & Proteomics
DOI: 10.21873/cgp.20513
Authors: CHIH-CHUN WANG, TZER-ZEN HWANG, CHING-FENG LIEN, YINGXIAO LI, YU-YAN LAN
Institutions: E-Da Hospital, I-Shou University
Language: English
Topic: Head and Neck Cancer Studies
Subfield: Otorhinolaryngology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4409800457