Related Experiment Video

Updated: Jul 2, 2025

Analysis of the c-KIT Ligand Promoter Using Chromatin Immunoprecipitation
09:40

Analysis of the c-KIT Ligand Promoter Using Chromatin Immunoprecipitation

Published on: June 27, 2017

7.8K

Crosstalk between KDEL receptor and EGF receptor mediates cell proliferation and migration via STAT3 signaling

Jie Jia1, Lianhui Zhu1, Xihua Yue1

  • 1School of Life Science and Technology, ShanghaiTech University, Pudong, Shanghai, China.

Cell Communication and Signaling : CCS
|February 20, 2024
PubMed

Insights

Secreted endoplasmic reticulum (ER) chaperones promote cancer growth. The KDEL receptor (KDELR) acts as a cell surface receptor, interacting with EGF receptor (EGFR) to activate STAT3 signaling, driving tumor cell proliferation and migration.

Area of Science:

  • Cell Biology
  • Cancer Research
  • Molecular Oncology

Background:

  • Cancer cells create a hostile microenvironment, stressing the endoplasmic reticulum (ER).
  • This stress stimulates ER chaperone expression and secretion, contributing to tumor progression.
  • The precise molecular mechanisms linking secreted chaperones to tumorigenesis are not fully understood.

Purpose of the Study:

  • To elucidate the molecular mechanism by which secreted ER chaperones promote cancer cell proliferation and migration.
  • To identify the cell surface receptor and signaling pathway involved in mediating these effects.

Main Methods:

  • Proximity-based mass spectrometry
  • Split Venus imaging
  • Membrane yeast two-hybrid assay

Main Results:

  • The KDEL motif of ER chaperones is crucial for mediating cell proliferation and migration.
  • Epidermal Growth Factor Receptor (EGFR) acts as a co-receptor for the KDEL Receptor (KDELR) on the cell surface.
  • KDELR interacts with EGFR upon ligand binding, leading to EGFR C-terminal tyrosine phosphorylation and STAT3 activation, which drives cell growth and migration.

Conclusions:

  • KDELR functions as a cell surface receptor for secreted ER chaperones.
  • Secreted ER chaperones activate the EGFR-STAT3 signaling pathway, promoting cancer progression.
  • Targeting the KDELR-EGFR-STAT3 axis may offer therapeutic strategies for cancer treatment.
Keywords:
ClathrinEGF receptorERp57EndosomesGRP78GolgiKDEL receptorSTAT3

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