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Molecular competition between plasminogen activator inhibitors type -1 and -2 for urokinase: implications for cellular proteolysis and adhesion in cancer

Journal Article


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Abstract


  • Up-regulation of the urokinase plasminogen activation (uPA) system leads to increased

    cancer invasion and metastasis. Plasminogen activator inhibitors type-1 (PAI-1/SERPINE1)

    and type-2 (PAI-2/SERPINB2) have similar uPA inhibitory properties yet PAI-1 promotes

    cell invasion by modulating cell adhesion and migration. High tumour PAI-2 levels are

    associated with improved prognoses. Herein we show that PAI-2 is capable of inhibiting

    uPA in the presence of PAI-1, particularly on adherent cells in the presence of vitronectin.

    This suggests that elevated levels of PAI-2 in the tumour microenvironment could outcompete

    PAI-1 for uPA inhibition through its inhibitory serpin function. However, PAI-1 modulated

    cell adhesion in a largely uPA-independent manner consequently PAI-2 could not

    counteract the effects of PAI-1 on adhesion/migration. Thus studies aimed at further characterising

    the interplay between PAI-1 and PAI-2 on uPA-dependent pro-invasive processes

    are warranted.

Authors


Publication Date


  • 2011

Citation


  • Lobov, S. & Ranson, M. (2011). Molecular competition between plasminogen activator inhibitors type -1 and -2 for urokinase: implications for cellular proteolysis and adhesion in cancer. Cancer Letters, 303 (2), 118-127.

Scopus Eid


  • 2-s2.0-79952041524

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1129&context=ihmri

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/114

Number Of Pages


  • 9

Start Page


  • 118

End Page


  • 127

Volume


  • 303

Issue


  • 2

Abstract


  • Up-regulation of the urokinase plasminogen activation (uPA) system leads to increased

    cancer invasion and metastasis. Plasminogen activator inhibitors type-1 (PAI-1/SERPINE1)

    and type-2 (PAI-2/SERPINB2) have similar uPA inhibitory properties yet PAI-1 promotes

    cell invasion by modulating cell adhesion and migration. High tumour PAI-2 levels are

    associated with improved prognoses. Herein we show that PAI-2 is capable of inhibiting

    uPA in the presence of PAI-1, particularly on adherent cells in the presence of vitronectin.

    This suggests that elevated levels of PAI-2 in the tumour microenvironment could outcompete

    PAI-1 for uPA inhibition through its inhibitory serpin function. However, PAI-1 modulated

    cell adhesion in a largely uPA-independent manner consequently PAI-2 could not

    counteract the effects of PAI-1 on adhesion/migration. Thus studies aimed at further characterising

    the interplay between PAI-1 and PAI-2 on uPA-dependent pro-invasive processes

    are warranted.

Authors


Publication Date


  • 2011

Citation


  • Lobov, S. & Ranson, M. (2011). Molecular competition between plasminogen activator inhibitors type -1 and -2 for urokinase: implications for cellular proteolysis and adhesion in cancer. Cancer Letters, 303 (2), 118-127.

Scopus Eid


  • 2-s2.0-79952041524

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1129&context=ihmri

Ro Metadata Url


  • http://ro.uow.edu.au/ihmri/114

Number Of Pages


  • 9

Start Page


  • 118

End Page


  • 127

Volume


  • 303

Issue


  • 2