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Updated: Jul 18, 2025

Cell Population Analyses During Skin Carcinogenesis
06:53

Cell Population Analyses During Skin Carcinogenesis

Published on: August 21, 2013

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Driver gene combinations dictate cutaneous squamous cell carcinoma disease continuum progression

Peter Bailey1,2,3, Rachel A Ridgway4, Patrizia Cammareri4,5

  • 1School of Cancer Sciences, University of Glasgow, Glasgow, G61 1QH, UK. Peter.Bailey.2@glasgow.ac.uk.

Nature Communications
|August 25, 2023
PubMed

Insights

Understanding cutaneous squamous cell carcinoma (cSCC) progression from actinic keratosis (AK) is crucial. This study maps the cSCC disease continuum, revealing key molecular events driving progression from differentiated to progenitor-like states.

Area of Science:

  • Oncology
  • Dermatology
  • Molecular Biology

Background:

  • The progression from actinic keratosis (AK) to invasive cutaneous squamous cell carcinoma (cSCC) and metastasis is poorly understood at a molecular level.
  • While DNA sequencing reveals high mutational burden, mechanisms driving cSCC progression remain elusive.

Purpose of the Study:

  • To elucidate the molecular mechanisms underlying the progression of UV-induced skin lesions to invasive and metastatic cutaneous squamous cell carcinoma (cSCC).
  • To identify key molecular events and cellular state transitions during cSCC development.

Main Methods:

  • RNA sequencing (RNAseq) transcriptomic profiling of 110 patient samples, including normal skin, AK, primary cSCC, and metastatic cSCC.
  • Comparative systems analysis of human cSCC and generation of genetically engineered murine models.

Main Results:

  • A disease continuum from differentiated to progenitor-like states was identified in cSCC progression.
  • Key events include suppression of epidermal differentiation regulators, modulation of the epidermal differentiation complex, immune landscape remodeling, and increased tumor-specific keratinocytes.
  • Combinatorial inactivation of Tgfbr2, Trp53, Notch1, and activation of Ras signaling drives cSCC progression along a differentiated-to-progenitor axis.

Conclusions:

  • This study provides a comprehensive molecular map of the cSCC disease continuum.
  • Identified actionable events and signaling pathways that promote and accompany cSCC progression, offering potential therapeutic targets.

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