Emerging roles of proteases in tumour suppression

Proteases have long been associated with cancer progression because of their ability to degrade extracellular matrices, which facilitates invasion and metastasis. However, recent studies

have shown that these enzymes target a diversity of substrates and favour all steps of tumour evolution. Unexpectedly, the post-trial studies have also revealed proteases with

tumour-suppressive effects. These effects are associated with more than 30 different enzymes that belong to three distinct protease classes. What are the clinical implications of these

findings?

We thank all members of our laboratories for their helpful comments on the manuscript and apologize for omission of relevant works owing to space constraints. We especially thank J.P.

Freije, X.S. Puente, G.R. Ordoñez and J. Quigley for helpful insights. C.L-O. is supported by grants from Ministerio de Educación y Ciencia, European Union, Fundación M. Botín, Fundación La

Caixa and Fundación Lilly. L.M. is supported by grants from the National Cancer Institute, US National Institutes of Health, the US Department of Defense, and the American Cancer Society.

The Instituto Universitario de Oncología is supported by Obra Social Cajastur-Asturias, Spain.

Carlos López-Otín is at the Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, 33006 Oviedo, Spain.,

Lynn M. Matrisian is at the Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee 37232-6840, USA.,

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