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MYC in mammalian epidermis: how can an oncogene stimulate differentiation?

Nature Reviews Cancer volume 8, pages 234–242 (2008)Cite this article

An Erratum to this article was published on 01 April 2008

Abstract

MYC in human epidermal stem cells can stimulate differentiation rather than uncontrolled proliferation. This discovery was, understandably, greeted with scepticism by researchers. However, subsequent studies have confirmed that MYC can stimulate epidermal stem cells to differentiate and have shed light on the underlying mechanisms. Two concepts that are relevant to cancer have emerged: first, MYC regulates similar genes in different cell types, but the biological consequences are context-dependent; and second, MYC activation is not a simple 'on/off' switch — the cellular response depends on the strength and duration of MYC activity, which in turn is affected by the many cofactors and regulatory pathways with which MYC interacts.

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Figure 1: Effect of MYC activation on murine skin.
Figure 2: Concept of MYC-induced terminal differentiation as a fail-safe mechanism to prevent uncontrolled proliferation of epidermal stem cells.
Figure 3: Summary of the different effects of MYC on the epidermal stem-cell compartment.
Figure 4: Reduction in epidermal hemidesmosome number and size on activation of MYC.
Figure 5: Schematic summary of the interplay between RAC1 and MYC in regulating the epidermal stem-cell and transit-amplifying-cell compartments.
Figure 6: Chromatin modification by MYC.

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Author information

Authors and Affiliations

  1. Fiona Watt is at the Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK and the Wellcome Trust Centre for Stem Cell Research, Tennis Court Road, Cambridge CB2 1QR, UK.,

    Fiona M. Watt

  2. Michaela Frye is at the Wellcome Trust Centre for Stem Cell Research.,

    Michaela Frye

  3. Salvador Aznar Benitah is at the Department of Cell Differentiation and Cancer, Center for Genomic Research, Biomedical Research Park (CRG-PRBB), Barcelona, Spain.,

    Salvador Aznar Benitah

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  1. Fiona M. Watt
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  2. Michaela Frye
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  3. Salvador Aznar Benitah
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Correspondence to Fiona M. Watt.

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Watt, F., Frye, M. & Benitah, S. MYC in mammalian epidermis: how can an oncogene stimulate differentiation?. Nat Rev Cancer 8, 234–242 (2008). https://doi.org/10.1038/nrc2328

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