J Turton

University of Newcastle, Newcastle, New South Wales, Australia

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Publications (6)27.07 Total impact

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    ABSTRACT: Expression of the growth-promoting integrin alphavbeta6 in colon cancer cells induces gelatinase B secretion and activation, the inhibition of which abolishes alphavbeta6-mediated tumour cell growth within a collagen matrix. Herein, we show that high cell density selectively enhances alphavbeta6 expression in a protein kinase C (PKC)-dependent manner in preference to other beta integrin subunits, resulting in a marked increase in gelatinase B secretion as cells reach confluence. Moreover, PKC activity increases with cell confluence, and the rise in PKC activity is much greater for alphavbeta6-expressing cells than for colon cancer cells which lack alphavbeta6. We propose a self-perpetuating system of colon cancer progression in which the integrin alphavbeta6 provides a means of sustaining tumour cell proliferation. In this model, alphavbeta6 regulates its own expression via a PKC-mediated signalling pathway as tumour cells become crowded and quiescent. The alphavbeta6-mediated induction of gelatinase B secretion facilitates peri-cellular matrix degradation, which helps overcome crowding and restores cell proliferation.
    International Journal of Cancer 05/2001; 92(1):40-8. · 6.20 Impact Factor
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    ABSTRACT: Expression of the growth-promoting integrin αvβ6 in colon cancer cells induces gelatinase B secretion and activation, the inhibition of which abolishes αvβ6-mediated tumour cell growth within a collagen matrix. Herein, we show that high cell density selectively enhances αvβ6 expression in a protein kinase C (PKC)–dependent manner in preference to other β integrin subunits, resulting in a marked increase in gelatinase B secretion as cells reach confluence. Moreover, PKC activity increases with cell confluence, and the rise in PKC activity is much greater for αvβ6-expressing cells than for colon cancer cells which lack αvβ6. We propose a self-perpetuating system of colon cancer progression in which the integrin αvβ6 provides a means of sustaining tumour cell proliferation. In this model, αvβ6 regulates its own expression via a PKC-mediated signalling pathway as tumour cells become crowded and quiescent. The αvβ6-mediated induction of gelatinase B secretion facilitates peri-cellular matrix degradation, which helps overcome crowding and restores cell proliferation. © 2001 Wiley-Liss, Inc.
    International Journal of Cancer 03/2001; 92(1):40 - 48. · 6.20 Impact Factor
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    ABSTRACT: In human cancers, the co-operative role between cell-adhesion receptors and proteases capable of degrading matrix barriers remains poorly understood. We have previously reported that the epithelium-restricted integrin vβ6 becomes highly expressed in colon cancer compared with normal mucosa and that heterologous expression of vβ6 in colon cancer cells is associated with enhanced cell growth. Herein, we report that vβ6 expression in colon cancer cells leads to a relative increase in secretion of the matrix metalloproteinase gelatinase B over its respective inhibitor and that this secretion parallels the level of cell-surface β6 expression. The vβ6-mediated gelatinase B secretion is associated with increased proteolysis of denatured collagen at the cell surface, and inactivation of gelatinase B in β6-expressing tumour cells inhibits cell spreading and proliferation within 3-dimensional collagen matrices. Our findings suggest that vβ6-mediated gelatinase B secretion is important in the progression of human colon cancer. Int. J. Cancer 81:90–97, 1999. © 1999 Wiley-Liss, Inc.
    International Journal of Cancer 11/1999; 81(1):90 - 97. · 6.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In human cancers, the co-operative role between cell-adhesion receptors and proteases capable of degrading matrix barriers remains poorly understood. We have previously reported that the epithelium-restricted integrin alpha(v)beta6 becomes highly expressed in colon cancer compared with normal mucosa and that heterologous expression of alpha(v)beta6 in colon cancer cells is associated with enhanced cell growth. Herein, we report that alpha(v)beta6 expression in colon cancer cells leads to a relative increase in secretion of the matrix metalloproteinase gelatinase B over its respective inhibitor and that this secretion parallels the level of cell-surface beta6 expression. The alpha(v)beta6-mediated gelatinase B secretion is associated with increased proteolysis of denatured collagen at the cell surface, and inactivation of gelatinase B in beta6-expressing tumour cells inhibits cell spreading and proliferation within 3-dimensional collagen matrices. Our findings suggest that alpha(v)beta6-mediated gelatinase B secretion is important in the progression of human colon cancer.
    International Journal of Cancer 04/1999; 81(1):90-7. · 6.20 Impact Factor
  • International Journal of Cancer - INT J CANCER. 01/1999; 81(1):90-97.
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    ABSTRACT: The progression of colon cancer has been linked to both cell adhesion molecules called integrins and matrix-degrading enzymes called metalloproteinases. Herein we report that the alpha v beta 6 integrin expressed in colon cancer cells induces gelatinase B secretion through the C-terminal cytoplasmic extension unique to the beta 6 integrin subunit, and that this ligand-independent event involves activation of the protein-kinase-C pathway.
    Biochemical and Biophysical Research Communications 09/1998; 249(1):287-91. · 2.28 Impact Factor

Publication Stats

133 Citations
27.07 Total Impact Points

Institutions

  • 1998–2001
    • University of Newcastle
      • Sub-discipline of General Surgery
      Newcastle, New South Wales, Australia
    • John Hunter Hospital
      New Lambton, New South Wales, Australia