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Updated: Dec 9, 2025

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KLF5-mediated COX2 upregulation contributes to tumorigenesis driven by PTEN deficiency

Liang Zhang1, Yuncui Wu2, Jing Wu1

  • 1Department of Otorhinolaryngology, Head & Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Cellular Signalling
|September 5, 2020
PubMed

Insights

Loss of the tumor suppressor PTEN increases cyclooxygenase-2 (COX2) via Krüppel-like factor 5 (KLF5). This KLF5/COX2/NOX4 pathway drives cancer cell growth, suggesting combination therapy for PTEN-deficient tumors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Signaling

Background:

  • The tumor suppressor gene PTEN is frequently altered in various cancers.
  • Downstream targets and signaling pathways of PTEN are not fully elucidated.

Purpose of the Study:

  • To investigate the downstream signaling pathways affected by PTEN loss.
  • To identify potential therapeutic targets for PTEN-deficient cancers.

Main Methods:

  • Analysis of Pten-null mouse embryonic fibroblasts (MEFs) and isogenic counterparts.
  • Gene expression analysis, including transcription factors and signaling molecules.
  • Cell proliferation, migration, and tumor growth assays.
  • Pharmacological inhibition of AKT and COX2 pathways.

Main Results:

  • PTEN loss increased cyclooxygenase-2 (COX2) expression independently of AKT signaling.
  • PTEN deficiency promoted COX2 transcription via upregulation of Krüppel-like factor 5 (KLF5).
  • COX2 knockdown suppressed proliferation, migration, and tumor growth in Pten-null cells.
  • COX2 enhanced growth and migration through NADPH oxidase 4 (NOX4) upregulation.
  • Combined inhibition of AKT (MK-2206) and COX2 (celecoxib) significantly reduced Pten-deficient cell growth.

Conclusions:

  • The KLF5/COX2/NOX4 signaling axis is crucial for cell proliferation and migration in PTEN-deficient contexts.
  • Combination therapy with AKT and COX2 inhibitors presents a promising strategy for treating PTEN-deficient tumors.
Keywords:
COX2CelecoxibKLF5MK-2206PTEN

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