title: Modulation of the urokinase-type plasminogen activator receptor by the beta6 integrin subunit.
abstract: Over-expression of components of the urokinase system is well documented in cancer and is thought to enable tumour cells to migrate and invade. Changes in integrin expression are also a common feature of tumours and have been linked to changes in protease activity. It has been shown that the alphavbeta6 integrin is neo-expressed in a number of epithelial carcinomas and in wound healing situations. We therefore investigated whether alphavbeta6 is able to modulate a key regulator of proteolysis, the urokinase receptor. We report that epithelial cells expressing full-length alphavbeta6 exhibit decreased urokinase receptor expression and function. Furthermore, this novel modulation requires the C-terminal 11 amino acids of the cytoplasmic tail of the beta6 integrin subunit. Cells expressing alphavbeta3, however, did not affect urokinase receptor expression. De novo expression of beta6 by melanoma cells and beta3 by epithelial cells did not influence urokinase receptor expression or function, suggesting that modulation of urokinase system is both integrin subunit and cell-specific.
authors.affiliation: Department of Oral Pathology, Eastman Dental Institute for Oral Health Care Sciences, University College London, London WC1X 8LD, UK. nafisa.dalvi@man.ac.uk
authors.forename: Nafisa
authors.initials: N
authors.lastname: Dalvi
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Thomas
authors.forename: John F
authors.initials: JF
authors.lastname: Marshall
authors.forename: Mark
authors.initials: M
authors.lastname: Morgan
authors.forename: Rosemary
authors.initials: R
authors.lastname: Bass
authors.forename: Vincent
authors.initials: V
authors.lastname: Ellis
authors.forename: Paul M
authors.initials: PM
authors.lastname: Speight
authors.forename: Simon A
authors.initials: SA
authors.lastname: Whawell
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D005341:Fibrinolysin / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D039641:Integrin beta Chains / Q000502:physiology*; D015603:Keratinocytes / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism; D009055:Mouth / Q000166:cytology; D009062:Mouth Neoplasms / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
chemical_list: D005353:Fibronectins; D039641:Integrin beta Chains; C524898:PLAUR protein, human; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; C072170:integrin beta6; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator