Convertases are widely expressed activating enzymes involved in various physiological and pathological processes. This book provides detailed and updated information on the role of these molecules in cancer. It is the first to summarize current knowledge of the importance of protein precursors maturation by the convertases in tumor progression, angiogenesis and metastasis. Each chapter discusses the importance of the convertases in the activation of various cancer-related molecules including growth factors, adhesion molecules and proteases.

Convertases are widely expressed activating enzymes involved in various physiological and pathological processes. This book provides detailed and updated information on the role of these molecules in cancer. It is the first to summarize current knowledge of the importance of protein precursors maturation by the convertases in tumor progression, angiogenesis and metastasis. Each chapter discusses the importance of the convertases in the activation of various cancer-related molecules including growth factors, adhesion molecules and proteases.

The vascular endothelial growth factor (VEGF) family members that include VEGF-A, -B, -C, -D, and placental growth factor (PlGF), display distinct binding affinities for their receptors VEGFR-1, -2, and/or -3. In addition to their requirements in the initiation, development, and maintenance of blood and lymphatic vasculature, VEGFs and VEGFRs are upregulated during neoplasia and are involved in the remodeling of tumoral blood and lymphatic vasculature. By activating VEGFR-1 and VEGFR-2, both expressed on blood endothelial cells, VEGF-A promotes the formation of new tumoral blood vessels and thereby accelerates tumor growth. In contrast, upregulation of VEGF-C, a ligand for lymphatic endothelial VEGFR-3 as well as for VEGFR-2, induces the formation of tumor-associated lymphatic vessels and thus promotes the passive metastatic dissemination of tumor cells to regional lymph nodes. Of the VEGF family members, only VEGF-C and -D were found to be proteolytically processed by Furin-like enzymes. This processing controls the selective activation of VEGFR-2 and -3 signaling during tumor angiogenesis and lymphangiogenesis. Here, we provide an overview of angiogenesis processes and discuss the importance of VEGF-C and VEGF-D precursors processing by the proprotein convertases during the activation of VEGFR-2 and VEGFR-3 receptors and the mediation of their functions during angiogenesis, lymphangiogenesis, and tumorigenesis.

Proprotein convertases (PCs) are a family of proteases including PC1, PC2, Furin, PC4, PACE4, PC5, and PC7. These enzymes are involved in the maturation of many precursor proteins involved in the process of tumorigenesis and metastasis. Since their discovery, PCs were suggested as potential targets for anti-cancer therapy, and their activity was found to directly affect tumor cell proliferation, migration invasion, and the malignant phenotypes of tumor cells. Here, we discuss a number of previous and recent findings on the PCs features, their implication in the regulation of multiple cellular functions that impact on the invasive/metastatic potential of cancer cells, and their clinical relevance in cancer patients. Among the substrates of the proprotein convertases, various growth factors, their receptors, adhesion molecules, and proteases were identified. The PCs are inhibited by endogenous and exogenous inhibitors. To date, only pro7B2, a specific chaperone of PC2, and the granine-like precursor of neuroendocrine protein proSAAS, a selective ligand of PC1, have been identified as endogenous inhibitors of the PCs found in the regulated pathway. However, only PCs prosegments, several bioengineered inhibitors, peptides, and non-peptide compounds were found to inhibit the activity of the PCs found in the secretory pathway.