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TMED2 Induces Cisplatin Resistance in Breast Cancer via Targeting the KEAP1-Nrf2 Pathway

Chen Liang1, Han-Yong Zhang2, Yi-Qian Wang1

  • 1College of Life Sciences and Health, Wuhan University of Science and Technology, Wuhan, 430070, China.

Current Medical Science
|August 24, 2023
PubMed
Abstract

Insights

Transmembrane emp24 protein transport domain containing 2 (TMED2) promotes cisplatin resistance in breast cancer by activating the Nrf2 pathway. This finding offers new insights into overcoming drug resistance in breast cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Cisplatin is a primary breast cancer treatment, but drug resistance limits its efficacy.
  • Understanding novel molecular mechanisms of cisplatin resistance is crucial for improving patient outcomes.

Purpose of the Study:

  • To investigate the role of transmembrane emp24 protein transport domain containing 2 (TMED2) in breast cancer cisplatin resistance.
  • To elucidate the molecular pathways through which TMED2 influences drug resistance.

Main Methods:

  • Analysis of TCGA database for TMED2 and breast cancer associations.
  • In vitro experiments using MCF-7 and MDA-MB-231 cell lines.
  • Western blotting, real-time PCR, CCK-8, and TUNEL assays to assess TMED2 function and molecular mechanisms.

Main Results:

  • TMED2 is overexpressed in breast cancer and correlates with poor prognosis.
  • TMED2 enhances cisplatin resistance by promoting KEAP1 ubiquitination, activating Nrf2.
  • Activated Nrf2 leads to increased expression of drug resistance genes (HO-1, NQO1).

Conclusions:

  • TMED2 represents a novel molecular target influencing cisplatin resistance in breast cancer.
  • The TMED2-KEAP1-Nrf2 pathway is a key mechanism driving chemoresistance.
  • Findings provide a theoretical basis for developing strategies to overcome cisplatin resistance.
Keywords:
KEAP1Nrf2TMED2breast cancercisplatin resistance

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