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Updated: Jun 21, 2026

Cell Population Analyses During Skin Carcinogenesis
06:53

Cell Population Analyses During Skin Carcinogenesis

Published on: August 21, 2013

Epidermal Notch1 loss promotes skin tumorigenesis by impacting the stromal microenvironment

Shadmehr Demehri1, Ahu Turkoz, Raphael Kopan

  • 1Department of Developmental Biology, Division of Dermatology, Washington University School of Medicine, Saint Louis, MO 63110-1095, USA.

Cancer Cell
|July 4, 2009
PubMed

Insights

Notch1 loss in skin cells promotes tumor growth by disrupting skin barrier integrity, creating a wound-like environment. This non-cell autonomous effect highlights Notch1

Area of Science:

  • Dermatology
  • Oncology
  • Cell Biology

Background:

  • Notch1 is typically a proto-oncogene, but its deletion in skin suggests a tumor suppressor role.
  • Skin tumor formation upon Notch1 deletion indicates a context-dependent function.

Purpose of the Study:

  • To investigate the mechanism by which Notch1 loss promotes skin tumorigenesis.
  • To determine if Notch1 acts as a classical tumor suppressor in the epidermis.

Main Methods:

  • Utilized mice with a chimeric pattern of Notch1 deletion in epidermal keratinocytes.
  • Analyzed the impact of Notch1 loss on skin barrier integrity and the dermal microenvironment.
  • Assessed tumor formation in Notch1-expressing keratinocytes within the altered microenvironment.

Main Results:

  • Notch1 loss in epidermal keratinocytes promotes tumorigenesis non-cell autonomously.
  • Impaired skin-barrier integrity and a wound-like microenvironment result from Notch1 deletion.
  • Notch1-expressing keratinocytes formed papillomas in the altered microenvironment, indicating Notch1 insufficiency to suppress tumors.
  • Loss of other Notch paralogues also impaired skin barrier and promoted tumorigenesis.

Conclusions:

  • Notch1 loss promotes skin tumorigenesis by compromising skin barrier function and altering the microenvironment.
  • The tumor-promoting effect of Notch1 loss involves crosstalk between a defective epidermis and its stroma.
  • Notch1's role in skin cancer is complex, acting differently than classical tumor suppressors.

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