Role of alpha6beta4 integrin in epidermal tumorigenesis

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Project objective

Keratinocytes are the main cell type of the epidermis. Several integrins are expressed in keratinocytes and mediate adhesion to the underlying extra cellular matrix and regulate the initiation of terminal differentiation and morphogenesis. Integrins are down regulated when keratinocytes are committed to differentiate and exit from the basal layer. But abnormal expression of integrins has been documented in many tumors. Although little is known about how integrins influence neoplastic progression, some integrins, as alpha6beta4, seem to be implicated in the generation of epidermal tumors. This abnormal integrin expression is the major interest of our project. We will try to test the role of alpha6beta4 integrin in the generation of epidermal tumors and the mechanism by which this effect occurs. We will generate mice expressing chimeric integrins with the different domains of alpha6 to study which domain, the extra cellular or the cytoplasmic, promotes tumor genesis. Furthermore, the generation of transgenic mice expressing alpha6beta4 in the differentiating layers of the epidermis will let us to discern about what mechanism is mediating this increased tumor genesis. We will do these studies in vivo, with the transgenic mice, and in vitro, with isolated keratinocytes from these animals.

Original text from CORDIS.

Participants

• CANCER RESEARCH UK · LONDONCoordinatorUnited Kingdom

Links

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