EMC2 suppresses ferroptosis via regulating TFRC in nasopharyngeal carcinoma

Xianghui Chen1, Xiaoyan Wang2, Yuxia Zou3

  • 1Shengli Clinical Medical College of Fujian Medical University, Department of Otolaryngology, Head and Neck Surgery, Fujian Provincial Hospital, Fuzhou 350001, China; Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350001, China.

Translational Oncology
|December 22, 2024
PubMed
Abstract

Insights

Endoplasmic reticulum membrane protein complex 2 (EMC2) suppresses ferroptosis and promotes nasopharyngeal carcinoma (NPC) progression. Targeting the EMC2-transferrin receptor (TFRC) axis offers a new therapeutic strategy for NPC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Death Research

Background:

  • Nasopharyngeal carcinoma (NPC) is an epithelial malignancy with incompletely understood molecular drivers.
  • Ferroptosis, a regulated cell death pathway, has not been fully characterized in the context of NPC.

Purpose of the Study:

  • To investigate the role of endoplasmic reticulum membrane protein complex 2 (EMC2) in NPC.
  • To elucidate the molecular mechanisms by which EMC2 influences ferroptosis and carcinogenesis in NPC.
  • To evaluate EMC2 as a potential biomarker and therapeutic target for NPC.

Main Methods:

  • Quantitative proteomics was employed to identify dysregulated proteins in NPC tissues.
  • Immunohistochemistry was used to assess EMC2 levels in NPC tissue microarrays.
  • In vitro and in vivo experiments were conducted to determine the function of EMC2 in ferroptosis and cancer progression.
  • Proteomics, protease inhibition, and ubiquitin detection assays explored the EMC2-mediated ferroptosis pathway.

Main Results:

  • EMC2 was significantly upregulated in NPC and correlated with tumor progression and poor patient survival.
  • EMC2 knockdown induced ferroptosis, reduced NPC cell viability, migration, and invasion, and enhanced cisplatin efficacy.
  • EMC2 overexpression repressed ferroptosis, promoted malignant progression, and decreased cisplatin sensitivity.
  • EMC2 interacted with transferrin receptor (TFRC), promoting its degradation and thereby regulating ferroptosis.

Conclusions:

  • EMC2 acts as a suppressor of ferroptosis and a promoter of NPC progression.
  • The EMC2-TFRC axis represents a novel pathway regulating ferroptosis in NPC.
  • EMC2 holds potential as a diagnostic biomarker and therapeutic target for nasopharyngeal carcinoma.

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