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First published online August 13, 2003

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Integrin 4ß6 and TGFß at odds in tumorigenesis

Squamous cell carcinomas in the skin arise from stem cells in the basal layer of the epidermis. Surprisingly, the suprabasal cells above frequently determine the severity of the disease: poor prognosis is associated with dysregulation of integrin 6ß4 in these cells rather than the basal stem cells below. Fiona Watt and co-workers have examined the basis for the correlation between 6ß4 dysregulation and tumor formation by creating transgenic mice that express 6ß4 in the suprabasal cells (see p. 3783). They demonstrate that these mice are highly susceptible to chemicals that induce tumors in the skin. Importantly, they also show that TGFß-mediated growth inhibition is compromised in keratinocytes from the mice: nuclear translocation of TGFß-responsive Smad signalling molecules is suppressed both in vivo and in an in vitro model. The authors find that the suppression of TGF-ß signalling can be relieved by PI 3-kinase (PI3K) inhibitors or a dominant negative mutant of the cell-cell adhesion protein E-cadherin. They therefore conclude that expression of integrin 6ß4 in the differentiated suprabasal cells unleashes the malignant potential of the undifferentiated basal cells by activating a PI3K- and cell-adhesion-dependent pathway that antagonizes the TGFß signal that normally prevents the basal cells from proliferating.

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Suprabasal 6ß4 integrin expression in epidermis results in enhanced tumourigenesis and disruption of TGFß signalling

David M. Owens, M. Rosario Romero, Clare Gardner, and Fiona M. Watt
JCS 2003 116: 3783-3791. [Abstract] [Full Text]  

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This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Search for Related Content