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Updated: Aug 24, 2025

Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate DMBA-TPA
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Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate DMBA-TPA

Published on: December 19, 2019

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Mutant Ras and inflammation-driven skin tumorigenesis is suppressed via a JNK-iASPP-AP1 axis

Khatoun Al Moussawi1, Kathryn Chung1, Thomas M Carroll1

  • 1Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7DQ, UK.

Cell Reports
|October 19, 2022
PubMed

Insights

Loss of iASPP, a p53 inhibitor, promotes skin tumor growth by altering inflammation and differentiation pathways. This study identifies a new JNK-iASPP-AP1 axis critical for maintaining tissue balance and tumor suppression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Dermatology

Background:

  • Concurrent RAS oncogene and p53 mutations are frequent in cancer.
  • Inflammation can drive RAS-induced tumorigenesis independently of p53 mutations.

Purpose of the Study:

  • To investigate the role of iASPP (inhibitor of AP-1 and STAT binding protein) in RAS-driven tumorigenesis.
  • To elucidate the mechanism by which iASPP loss influences skin tumor development and the tumor microenvironment.

Main Methods:

  • Utilized a mouse skin tumor model with mutant RAS and induced inflammation.
  • Analyzed the regulation of p63 and AP1 target genes by iASPP.
  • Investigated the role of JNK-mediated phosphorylation in iASPP function and AP1 interaction.

Main Results:

  • Loss of iASPP accelerates tumorigenesis in the studied model.
  • iASPP regulates genes involved in skin differentiation and inflammation.
  • JNK phosphorylation inhibits iASPP binding to AP1 components (e.g., JUND) via PXXP/SH3 interaction.

Conclusions:

  • iASPP acts as a tumor suppressor in skin carcinogenesis.
  • A novel JNK-iASPP-AP1 regulatory axis is identified, crucial for tissue homeostasis.
  • Loss of iASPP promotes a tumor-promoting inflammatory microenvironment.
Keywords:
AP1/JNKCP: CancerRASiASPPinflammation-driven tumorigenesisp63skin cancertarget selective transcription

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