The dipeptidyl peptidase IV family in cancer and cell biology

Abstract

Of the 600+ known proteases identified to date in mammals, a significant percentage is involved or implicated in pathogenic and cancer processes. The dipeptidyl peptidase IV (DPIV) gene family, comprising four enzyme members [DPIV (EC 3.4.14.5), fibroblast activation protein, DP8 and DP9] and two nonenzyme members [DP6 (DPL1) and DP10 (DPL2)], are interesting in this regard because of their multiple diverse functions, varying patterns of distribution/localization and subtle, but significant, differences in structure/substrate recognition. In addition, their engagement in cell biological processes involves both enzymatic and nonenzymatic capabilities. This article examines, in detail, our current understanding of the biological involvement of this unique enzyme family and their overall potential as therapeutic targets.

Contribution of upregulated dipeptidyl peptidase 9 (DPP9) in promoting tumoregenicity, metastasis and the prediction of poor prognosis in non‐small cell lung cancer (NSCLC)

“…The predominant reason for carcinogenesis can be attributed to the down‐regulation of tumor suppressor genes and the up‐regulation of oncogenes or cancer‐promoting genes 20. The DPP4 enzyme family is expressed and is found in all normal human adult and neonatal tissues 21, 22, 23…”

Clinical Implications of Marker Expression of Carcinoma-Associated Fibroblasts (CAFs) in Patients with Epithelial Ovarian Carcinoma After Treatment with Neoadjuvant Chemotherapy

“…FAP/seprase belongs to the family of plasma membrane-bound serine proteinases [19]. It is located at 2q23 and possesses gelatinolytic and collagenolytic activity as well as dipeptidyl peptidase activity, which have been implicated in matrix digestion and invasion [20]. FAP is expressed in reactive cancer-associated fibrosis and granulation tissue in healing wounds while absent in normal adult tissues, and thus is a highly specific marker of CAFs [10,19,20].…”

Food protein hydrolysates as a source of dipeptidyl peptidase IV inhibitory peptides for the management of type 2 diabetes

“…The application of natural compounds that inhibit the activity of this enzyme could represent a useful strategy to increase the half-life of active incretin hormones. suggests that it is associated with a variety of physiological functions including immunoregulation (44) , endocrine activity and the degradation of peptide hormones (45) . The immunological activities of DPP-IV such as T-cell stimulation, which rely on protein binding, are mediated by the external surface of the enzyme (46) .…”