Endo/exo-proteolysis in neoplastic progression and metastasis.

Abstract

Biological control of individual cells, organs, and organisms is achieved through interplay of a host of specific interactions that involve various peptidic molecules as modulators or effectors. In tumor cells, these processes may result in uncontrolled growth as a consequence of autocrine and/or paracrine actions. In recent years, growing evidence has accumulated for the important role of proprotein convertases (PCs) and peptide alpha-amidation enzymes in these processes. The widespread belief that these enzymes are involved in the major features of tumor progression, namely, invasiveness and metastasis, has taken place because of their capacity to process and activate many protein precursors involved in the neoplastic progression and metastasis. This includes degrading extracellular matrix proteases, growth promoting factors, and adhesion molecules. Usually, when the processing of these precursor proteins is achieved by one or more of the known PC family members within the general motif (K/R)-(X)n-(K/R) downward arrow, where n=0, 2, 4, or 6, and X, any amino acid except Cys, the accomplishment of the maturation of these molecules is attained by various posttranslational modifications, including the carboxy-terminal alpha-amidation. This review article summarizes recent findings on the role of these enzymatic systems in multiple cellular functions that impact on the invasive/metastatic potential of cancer cells and highlight the potential use of their inhibitors in the treatment of multiple cancers.

• Authors: Abdel-Majid Khatib, Daniel Bassi, Geraldine Siegfried, Andres J P Klein-Szanto, L'Houcine Ouafik
• Journal: Journal of molecular medicine (Berlin, Germany) (J Mol Med (Berl)) Vol. 83 Issue 11 Pg. 856-64 (Nov 2005) ISSN: 0946-2716 [Print] Germany
• PMID: 16133424 (Publication Type: Journal Article, Review)

Chemical References

• Multienzyme Complexes
• Peptides
• Mixed Function Oxygenases
• peptidylglycine monooxygenase
• Proprotein Convertases

Topics

• Cell Transformation, Neoplastic
• Humans
• Mixed Function Oxygenases (metabolism)
• Multienzyme Complexes (metabolism)
• Neoplasm Invasiveness
• Neoplasms (enzymology, therapy)
• Peptides (pharmacology)
• Proprotein Convertases (antagonists & inhibitors, physiology)