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Updated: Nov 12, 2025

A Quantitative Measurement of Reactive Oxygen Species and Senescence-associated Secretory Phenotype in Normal Human Fibroblasts During Oncogene-induced Senescence
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A Quantitative Measurement of Reactive Oxygen Species and Senescence-associated Secretory Phenotype in Normal Human Fibroblasts During Oncogene-induced Senescence

Published on: August 12, 2018

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COX2 regulates senescence secretome composition and senescence surveillance through PGE2

Susana Gonçalves1, Kelvin Yin1, Yoko Ito1

  • 1CRUK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK.

Cell Reports
|March 17, 2021
PubMed

Insights

Cyclooxygenase-2 (COX2) regulates the inflammatory SASP and immune surveillance of senescent cells. This COX2-prostaglandin E2 pathway is crucial for tumor suppression during early tumorigenesis.

Area of Science:

  • Cellular senescence
  • Immunology
  • Cancer biology

Background:

  • Senescent cells are cleared by immune surveillance, a process dependent on the senescence-associated secretory phenotype (SASP).
  • Cyclooxygenase-2 (COX2) is an enzyme within the SASP, but its role in senescence surveillance is unclear.
  • Understanding COX2's function in senescence is vital for cancer prevention.

Purpose of the Study:

  • To investigate the role of COX2 in regulating SASP composition and senescence surveillance during RAS-induced senescence (RIS).
  • To elucidate the molecular mechanisms by which COX2 influences the immune microenvironment during early tumorigenesis.

Main Methods:

  • In vivo studies of RAS-induced senescence in hepatocytes.
  • Analysis of SASP components, including COX2 and prostaglandin E2 (PGE2).
  • Assessment of immune cell populations and their functions within the tumor microenvironment.

Main Results:

  • COX2 is essential for regulating SASP composition and promoting senescence surveillance during RIS in vivo.
  • COX2 controls inflammatory SASP components via an autocrine loop involving PGE2 and EP4 signaling.
  • Loss of COX2 impairs tumor suppression, alters Cxcl1 expression, and leads to an immunosuppressive intrahepatic immune microenvironment.

Conclusions:

  • COX2 and its product PGE2 are critical regulators of senescence surveillance and tumor suppression.
  • The COX2-PGE2 pathway shapes SASP composition and influences the immune microenvironment during early tumorigenesis.
  • Targeting COX2 may offer therapeutic strategies for preventing cancer initiation.
Keywords:
COX2SASPimmune surveillanceliversenescence

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