Revisiting the biological roles of PAI2 (SERPINB2) in cancer.
Tumour expression of the urokinase plasminogen activator correlates with invasive capacity. Consequently, inhibition of this serine protease by physiological inhibitors should decrease invasion and metastasis. However, of the two main urokinase inhibitors, high tumour levels of the type 1 inhibitor actually promote tumour progression, whereas high levels of the type 2 inhibitor decrease tumour growth and metastasis. We propose that the basis of this apparently paradoxical action of two similar serine protease inhibitors lies in key structural differences controlling interactions with components of the extracellular matrix and endocytosis-signalling co-receptors.
Cancer Research Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales, Australia 2010.
David R
DR
Croucher
Darren N
DN
Saunders
Sergei
S
Lobov
Marie
M
Ranson
D000818:Animals; D006801:Humans; D006868:Hydrolysis; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D010958:Plasminogen / Q000378:metabolism; D017396:Plasminogen Activator Inhibitor 2 / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D011487:Protein Conformation
D017396:Plasminogen Activator Inhibitor 2; D010958:Plasminogen