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(American Journal of Pathology. 2002;160:1921-1935.)
© 2002 American Society for Investigative Pathology

Review

Proprotein Convertases in Tumor Progression and Malignancy

Novel Targets in Cancer Therapy

Abdel-Majid Khatib^*, Géraldine Siegfried^*, Michel Chrétien, Peter Metrakos and Nabil G. Seidah^*

From the Laboratory of Biochemical Neuroendocrinology,^*Clinical Research Institute of Montreal, Montreal, Quebec; Molecular Medicine and Disease of Aging Center,Loeb Health Research Institute, Ottawa Civic Hospital, Ottawa, Ontario; and the Departments of Surgery and Medicine,McGill University and the Royal Victoria Hospital, Montreal, Quebec, Canada

Abstract

The mammalian subtilisin/kexin-like proprotein convertase (PC) family has been implicated in the activation of a wide spectrum of proteins. These proteins are usually synthesized as inactive precursors before their conversion to fully mature bioactive forms. A large majority of these active proteins such as matrix metalloproteases, growth factors, and adhesion molecules are crucial in the processes of cellular transformation, acquisition of the tumorigenic phenotype, and metastases formation. Inhibition of PCs significantly affects the malignant phenotype of various tumor cells. In addition to direct tumor cell proliferation and migration blockade, PC inhibitors can also be used to target tumor angiogenesis. In this Review article we discuss a number of recent findings on the clinical relevance of PCs in cancer patients, their implication in the regulation of multiple cellular functions that impact on the invasive/metastatic potential of cancer cells. Thus, PC inhibitors may constitute new promising agents for the treatment of multiple tumors and/or in adjuvant therapy to prevent recurrence.

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