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

Abstract

Dipeptidyl peptidase 9 (DPP9) is encoded by DPP9, which belongs to the DPP4 gene family. Proteins encoded by these genes have unique peptidase and extra‐enzymatic functions that have been linked to various diseases including cancers. Here, we describe the expression pattern and biological function of DPP9 in non‐small‐cell lung cancer (NSCLC). The repression of DPP9 expression by small interfering RNA inhibited cell proliferation, migration, and invasion. Moreover, we explored the role of DPP9 in regulating epithelial‐mesenchymal transition (EMT). The epithelial markers E‐cadherin and MUC1 were significantly increased, while mesenchymal markers vimentin and S100A4 were markedly decreased in DPP9 knockdown cells. The downregulation of DPP9 in the NSCLC cells induced the expression of apoptosis‐associated proteins both in vitro and in vivo. We investigated the protein expression levels of DPP9 by tissue microarray immunohistochemical assay (TMA‐IHC) (n = 217). Further we found mRNA expression levels of DPP9 in 30 pairs of clinical NSCLC tissues were significantly lower than in the adjacent non‐cancerous tissues. Survival analysis showed that the overexpression of DPP9 was a significant independent factor for poor 5‐year overall survival in patients with NSCLC (p = 0.003). Taken together, DPP9 expression correlates with poor overall survival in NSCLC.

Structures and mechanism of dipeptidyl peptidases 8 and 9, important players in cellular homeostasis and cancer

“…The outcome of this processing and formation of a neo N terminus may alter the life span or activity of a variety of proteins (15,18). They are a focus of attention because of their relevance in immune response and cancer (9,11,(18)(19)(20)46). Therefore, molecular structures of both targets are a valuable basis for development of specific inhibitors.…”

“…Recently, the spleen tyrosine kinase (Syk) was shown to be processed by DPP9, thereby regulating B cell signaling (18). DPP9 activity is also connected to pathophysiological conditions, as promoting tumoregenicity and metastasis in nonsmall cell lung cancer (19). Recently, DPP9 fusion genes were identified in highgrade serous ovarian carcinoma, suggesting that DPP9 rearrangements might play a role in tumorigenesis or tumor progression (20).…”

<p>Fibroblast Activation Protein (FAP) Overexpression Induces Epithelial–Mesenchymal Transition (EMT) in Oral Squamous Cell Carcinoma by Down-Regulating Dipeptidyl Peptidase 9 (DPP9)</p>

“…34 found upregulated DPP9 promotes tumorgenicity and EMT in non-small cell lung cancer (NSCLC). This difference may FAP/DPP9 regulated EMT so as to regulate migration and EMT in OSCC cells.…”

A Glycolysis-Based Three-Gene Signature Predicts Survival in Patients with Lung Squamous Cell Carcinoma

“…For example, a study made by Tang and his colleagues found that the overexpression of dipeptidyl peptidase 9 (DPP9) was a signi cant independent factor for poor prognosis in patients with NSCLC. 10 Similarly, Feng et al 11 reported that high expression of forkhead box Q1 (FoxQ1) was associated with the poor prognosis in patients with NSCLC. However, the expression level of single gene can be in uenced by multiple factors, making these biomarkers hard to be reliable and independent prognosis indications in clinical.…”