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Emerging roles of proteases in tumour suppression

Abstract

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?

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Figure 1: Classification of human proteases.
Figure 2: Distribution of tumour-protective proteases in the human degradome.
Figure 3: Functional roles of anti-tumour proteases at different stages of cancer progression.
Figure 4: Substrates targeted by anti-tumour proteases.

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Acknowledgements

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.

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López-Otín, C., Matrisian, L. Emerging roles of proteases in tumour suppression. Nat Rev Cancer 7, 800–808 (2007). https://doi.org/10.1038/nrc2228

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