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Updated: Jul 11, 2026

Quantitative Measurement of γ-Secretase-mediated Amyloid Precursor Protein and Notch Cleavage in Cell-based Luciferase Reporter Assay Platforms
06:40

Quantitative Measurement of γ-Secretase-mediated Amyloid Precursor Protein and Notch Cleavage in Cell-based Luciferase Reporter Assay Platforms

Published on: January 25, 2018

Epidermal growth factor receptor and notch pathways participate in the tumor suppressor function of gamma-secretase

Tong Li1, Hongjin Wen, Cory Brayton

  • 1Department of Pathology, The Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205, USA. tli1@jhmi.edu

The Journal of Biological Chemistry
|September 11, 2007
PubMed

Insights

Gamma-secretase acts as a tumor suppressor by regulating epidermal growth factor receptor (EGFR) signaling. Reduced gamma-secretase activity leads to EGFR activation and hyperproliferation, contributing to squamous cell carcinoma (SCC) development.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cellular Signaling

Background:

  • Gamma-secretase is crucial for Notch and APP processing, implicated in cancer and Alzheimer's disease.
  • The mechanism by which reduced gamma-secretase activity promotes tumors like squamous cell carcinoma (SCC) is not fully understood.

Purpose of the Study:

  • To investigate the role of gamma-secretase as a tumor suppressor in epithelia.
  • To elucidate the mechanism linking gamma-secretase reduction to SCC pathogenesis, focusing on EGFR and Notch signaling.

Main Methods:

  • Genetic reduction of gamma-secretase in mouse models.
  • Analysis of Notch signaling and EGFR activation in SCC.
  • Assessment of fibroblast proliferation in response to EGF and EGFR inhibitors.

Main Results:

  • Gamma-secretase functions as a tumor suppressor in an enzyme activity-dependent manner.
  • Reduced gamma-secretase leads to EGFR activation and hyperproliferation, independent of Notch signaling.
  • Fibroblasts with reduced gamma-secretase show heightened sensitivity to EGF and EGFR inhibitors.

Conclusions:

  • A novel mechanism links the EGFR pathway to the tumor-suppressive function of gamma-secretase.
  • Mice with reduced gamma-secretase are a valuable model for SCC pathogenesis and therapeutic strategy development.

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