Dipeptidyl peptidase IV: a multifunctional enzyme with implications in several pathologies including cancer

Abstract

Abstract Ectopeptidases are particularly interesting due to their potential to regulate/dysregulate the peptide mediated signaling cellular pathways because the active site located to the extracellular space. Dipeptidyl peptidase IV (DPP-IV, EC 3.4.14.5) is currently one of the ectopeptidases that has a great and complex influence on important physiological and pathological processes. Due to its influence on the immune system, type 2 diabetes mellitus, pulmonary pathologies, cardiovascular system, viral infections and cancer, DPP-IV is very attractive as a possible therapeutic target. However, its versatility makes such expectations very difficult. The aim of this work is to summarize relevant structural and functional aspects of DPP-IV and the role of this protein in several pathologies with special emphasis on cancer. DPP-IV role in cancer seems to depend on specific location, histologic type of tumour, tumour microenvironment, and presence/absence of molecules able to interact with DPP-IV. Because of DPP-IV controversial effects, generalizations are difficult and most of the time the role of DPP-IV must be analyzed case by case. However, new evidences in cell lines, animal models and clinical studies suggest that DPP-IV inhibitors open a promissory window through new therapeutic strategies against some cancers.