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Proteomic profiling reveals that DPP4 overexpression increases cell adhesion, inhibits cell migration, and restores androgen sensitivity in prostate cancer.

José María Mora-Rodríguez·Belén G Sánchez·Alicia Bort·Alba Díaz-Yuste·Alicia Milla·Julie Courraud·Jerome Zoidakis·Inés Díaz-Laviada
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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.

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MaleDipeptidyl Peptidase 4AnimalsHumansCell MovementCell AdhesionProteomicsMiceCell Line, TumorGene Expression Regulation, NeoplasticProstatic Neoplasms, Castration-ResistantAndrogensCapsaicinReceptors, AndrogenEpithelial-Mesenchymal TransitionSignal TransductionCD26Dipeptidyl peptidase 4androgen resistancecapsaicinprostate cancerJournal Article

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José María Mora-Rodríguez, Belén G Sánchez, Alicia Bort, Alba Díaz-Yuste, Alicia Milla, Julie Courraud, Jerome Zoidakis, Inés Díaz-Laviada. 2026-09-16. Proteomic profiling reveals that DPP4 overexpression increases cell adhesion, inhibits cell migration, and restores androgen sensitivity in prostate cancer.. https://doi.org/10.1042/bsr20260054

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Journal Article resourceAndrogens subjectAnimals subjectCell Line, Tumor subjectCell Movement subjectGene Expression Regulation, Neoplastic subjectHumans subjectJournal Article subjectMale subjectMice subjectProstate cancer subjectProstatic Neoplasms, Castration-Resistant subject

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