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Published on: August 19, 2025
Proteomic profiling reveals that DPP4 overexpression increases cell adhesion, inhibits cell migration, and restores
José María Mora-Rodríguez1,2, Belén G Sánchez1,2, Alicia Bort1,2
1University of Alcalá, School of Medicine and Health Sciences, Department of Systems Biology, Biochemistry and Molecular Biology Unit, 28871 Alcalá de Henares, Madrid, Spain.
Abstract:
Dipeptidyl peptidase-4 (DPP4), a serine protease with both enzymatic and non-enzymatic roles, has emerged as a context-dependent modulator of tumor progression. In the present study, we investigated the expression and function of DPP4 in androgen-sensitive and castration-resistant prostate cancer (CRPC) models. Proteomic analysis of androgen-resistant prostate cells overexpressing DPP4 identified the involvement of the cellular adhesion molecules pathway. In prostate cells, lentiviral-mediated DPP4 overexpression restored androgen receptor signaling, inhibited epithelial-to-mesenchymal transition, and reduced cell migration, whereas DPP4 silencing produced the opposite effects. We demonstrate that DPP4 expression is down-regulated in CRPC cells and that treatment with capsaicin (CAP), a bioactive compound derived from red peppers, restores DPP4 expression. Moreover, DPP4 restoration by CAP suppresses prostate tumorigenesis in the TRAMP mice in vivo model of prostate cancer. Our results suggest that DPP4 could be a new target for CRPC.
Insights
Dipeptidyl peptidase-4 (DPP4) is downregulated in castration-resistant prostate cancer (CRPC). Restoring DPP4 with capsaicin inhibits prostate cancer progression and suggests DPP4 as a potential therapeutic target for CRPC.
Area of Science:
- Oncology
- Biochemistry
- Molecular Biology
Background:
- Dipeptidyl peptidase-4 (DPP4) is a serine protease involved in tumor progression.
- Its role in prostate cancer, particularly castration-resistant prostate cancer (CRPC), is not fully understood.
Purpose of the Study:
- To investigate the expression and function of DPP4 in androgen-sensitive and androgen-resistant prostate cancer models.
- To explore DPP4 as a potential therapeutic target for CRPC.
Main Methods:
- Proteomic analysis of prostate cancer cells.
- Lentiviral-mediated DPP4 overexpression and silencing.
- In vivo studies using TRAMP mice model.
- Treatment with capsaicin.
Main Results:
- DPP4 overexpression restored androgen receptor (AR) signaling, inhibited epithelial-to-mesenchymal transition (EMT), and reduced cell migration in prostate cells.
- DPP4 expression was found to be downregulated in CRPC cells.
- Capsaicin treatment restored DPP4 expression and suppressed prostate tumorigenesis in vivo.
- DPP4 restoration by capsaicin inhibited cellular adhesion molecule pathways.
Conclusions:
- DPP4 plays a context-dependent role in prostate cancer progression.
- DPP4 downregulation is observed in CRPC.
- Capsaicin can restore DPP4 expression and inhibit prostate cancer growth.
- DPP4 represents a promising therapeutic target for CRPC.
