Slug regulates integrin expression and cell proliferation in human epidermal keratinocytes

Frances Lock, S Broad, Farhat Khanim, A Jeanes, S Talma, Sharon Hughes, Chris Tselepis, Neil Hotchin

Research output: Contribution to journalArticlepeer-review

71 Citations (Scopus)


The human epidermis is a self-renewing epithelial tissue composed of several layers of keratinocytes. Within the epidermis there exists a complex array of cell adhesion structures, and many of the cellular events within the epidermis (differentiation, proliferation, and migration) require that these adhesion structures be remodeled. The link between cell adhesion, proliferation, and differentiation within the epidermis is well established, and in particular, there is strong evidence to link the process of terminal differentiation to integrin adhesion molecule expression and function. In this paper, we have analyzed the role of a transcriptional repressor called Slug in the regulation of adhesion molecule expression and function in epidermal keratinocytes. We report that activation of Slug, which is expressed predominantly in the basal layer of the epidermis, results in down-regulation of a number of cell adhesion molecules, including E-cadherin, and several integrins, including alpha 3, beta 1, and beta 4. We demonstrate that Slug binds to the alpha 3 promoter and that repression of alpha 3 transcription by Slug is dependent on an E-box sequence within the promoter. This reduction in integrin expression is reflected in decreased cell adhesion to fibronectin and laminin-5. Despite the reduction in integrin expression and function, we do not observe any increase in differentiation. We do, however, find that activation of Slug results in a significant reduction in keratinocyte proliferation.
Original languageEnglish
Pages (from-to)21321-21331
Number of pages11
JournalJournal of Biological Chemistry
Issue number30
Publication statusPublished - 9 Jun 2006

Bibliographical note

PubMed publication date shown as 28 July 2006


Dive into the research topics of 'Slug regulates integrin expression and cell proliferation in human epidermal keratinocytes'. Together they form a unique fingerprint.

Cite this