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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 contribution
posted on 2024-11-14, 20:54 authored by Sergei Lobov, Marie RansonMarie Ranson
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.

History

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.

Journal title

Cancer Letters

Volume

303

Issue

2

Pagination

118-127

Language

English

RIS ID

37576

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