Outside-in signaling through integrins and cadherins: a central mechanism to control epidermal growth and differentiation?

Müller, Eliane J; Williamson, Lina; Kolly, Carine; Suter, Maja M (2008). Outside-in signaling through integrins and cadherins: a central mechanism to control epidermal growth and differentiation? Journal of Investigative Dermatology, 128(3), pp. 501-16. New York, N.Y.: Nature Publishing 10.1038/sj.jid.5701248

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The process of epidermal renewal persists throughout the entire life of an organism. It begins when a keratinocyte progenitor leaves the stem cell compartment, undergoes a limited number of mitotic divisions, exits the cell cycle, and commits to terminal differentiation. At the end of this phase, the postmitotic keratinocytes detach from the basement membrane to build up the overlaying stratified epithelium. Although highly coordinated, this sequence of events is endowed with a remarkable versatility, which enables the quiescent keratinocyte to reintegrate into the cell cycle and become migratory when necessary, for example after wounding. It is this versatility that represents the Achilles heel of epithelial cells allowing for the development of severe pathologies. Over the past decade, compelling evidence has been provided that epithelial cancer cells achieve uncontrolled proliferation following hijacking of a "survival program" with PI3K/Akt and a "proliferation program" with growth factor receptor signaling at its core. Recent insights into adhesion receptor signaling now propose that integrins, but also cadherins, can centrally control these programs. It is suggested that the two types of adhesion receptors act as sensors to transmit extracellular stimuli in an outside-in mode, to inversely modulate epidermal growth factor receptor signaling and ensure cell survival. Hence, cell-matrix and cell-cell adhesion receptors likely play a more powerful and wide-ranging role than initially anticipated. This Perspective article discusses the relevance of this emerging field for epidermal growth and differentiation, which can be of importance for severe pathologies such as tumorigenesis and invasive metastasis, as well as psoriasis and Pemphigus vulgaris.

Item Type:

Journal Article (Original Article)


05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology

UniBE Contributor:

Müller, Eliane Jasmine, Williamson Ramirez, Lina, Kolly, Carine, Suter, Maja




Nature Publishing




Factscience Import

Date Deposited:

04 Oct 2013 14:54

Last Modified:

05 Dec 2022 14:16

Publisher DOI:


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Web of Science ID:



https://boris.unibe.ch/id/eprint/23100 (FactScience: 39216)

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