Related Experiment Video

Updated: May 30, 2025

Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis
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Characterization of MLKL-mediated Plasma Membrane Rupture in Necroptosis

Published on: August 7, 2018

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CHMP4C promotes pancreatic cancer progression by inhibiting necroptosis via the RIPK1/RIPK3/MLKL pathway

Longchen Yu1, Qining Guo1, Yaping Li1

  • 1Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan 250012 China; Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012 China.

Journal of Advanced Research
|January 27, 2025
PubMed
Abstract

Insights

CHMP4C promotes pancreatic cancer (PC) growth by inhibiting necroptosis, a cell death pathway. Targeting CHMP4C could offer new therapeutic strategies for this aggressive cancer.

Area of Science:

  • Oncology
  • Cell Death Mechanisms
  • Molecular Biology

Background:

  • Pancreatic cancer (PC) has a poor prognosis and lacks complete cures.
  • Necroptosis, a form of regulated cell death, presents a potential therapeutic target.
  • Understanding necroptosis in PC progression is crucial for developing new treatments.

Purpose of the Study:

  • To investigate the role of necroptosis in pancreatic cancer progression.
  • To elucidate the mechanisms by which necroptosis influences PC.
  • To identify potential therapeutic targets related to necroptosis in PC.

Main Methods:

  • RNA sequencing to identify differentially expressed necroptosis-related genes in PC.
  • In vitro and in vivo studies to assess the function of CHMP4C in PC and necroptosis.
  • Molecular assays (RNA immunoprecipitation, Co-immunoprecipitation) to analyze interactions involving CHMP4C, YBX1, and caspase-8 mRNA.
  • Analysis of CHMP4C, p-MLKL, and CD117 expression in PC tissues using multiplex immunofluorescence.

Main Results:

  • CHMP4C is overexpressed in PC, promoting tumor growth and suppressing necroptosis.
  • CHMP4C interacts with YBX1 to modify caspase-8 mRNA, increasing its expression and inhibiting the RIPK1/RIPK3/MLKL pathway.
  • CHMP4C facilitates the exocytosis of p-MLKL via extracellular vesicles, further inhibiting necroptosis.
  • PC cells utilize CHMP4C in extracellular vesicles to stimulate mast cells, enhancing tumor proliferation.
  • High CHMP4C expression correlates with poor survival outcomes in PC patients.

Conclusions:

  • CHMP4C drives pancreatic cancer progression by inhibiting necroptosis.
  • CHMP4C represents a potential biomarker for PC prognosis.
  • CHMP4C is a promising therapeutic target for pancreatic cancer treatment.
Keywords:
BiomarkerCHMP4CExtracellular vesiclesNecroptosisPancreatic cancer

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