DUSP13 promotes prostate cancer progression by regulating the ERK1/2 pathway

Prostate cancer (PCa) remains a leading cause of cancer-related morbidity and mortality in men, and patients who progress to castration-resistant prostate cancer (CRPC) derive only limited benefit from currently available treatments; novel therapeutic targets are therefore urgently needed. Dual specificity phosphatase 13 (DUSP13) belongs to the DUSP family, whose members dephosphorylate mitogen-activated protein kinases (MAPKs) and display either tumor-suppressive or tumor-promoting activity in a context-dependent manner. Emerging evidence implicates DUSP13 in several malignancies, but its expression and function in PCa, and whether it acts through the ERK1/2 pathway, remain unknown. This study aimed to elucidate the function of DUSP13 in PCa.

DUSP13 expression in the normal prostate epithelial-derived cell line RWPE-1 and in the PCa cell lines PC-3, DU145 and LNCaP was examined by Western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR). DUSP13 was silenced in PC-3 and DU145 cells using lentiviral short hairpin RNAs (shRNAs); a second, independent shRNA targeting a distinct site was used to exclude off-target effects. Cell proliferation, migration, invasion and apoptosis were assessed by cell counting kit-8 (CCK-8), wound-healing (scratch), transwell and flow cytometry assays, respectively. Tumor growth was evaluated in a PC-3 subcutaneous xenograft model in BALB/c nude mice. Proteins of the ERK1/2 pathway were detected by Western blot, and the MAPK/ERK kinase (MEK) inhibitor PD98059 was used in rescue experiments.

DUSP13 protein and mRNA levels were higher in PCa cells than in RWPE-1 cells. DUSP13 knockdown suppressed proliferation, migration and invasion, promoted apoptosis, and attenuated xenograft tumor growth in vivo. Mechanistically, DUSP13 knockdown increased p-ERK1/2 levels, whereas PD98059 alone did not significantly alter proliferation, invasion or apoptosis and partially reversed the anti-tumor phenotypes induced by DUSP13 knockdown. All key findings were reproduced with a second independent shRNA.

DUSP13 promotes PCa progression by inhibiting ERK1/2 phosphorylation, suggesting that targeting DUSP13 may be a potential therapeutic strategy for PCa, including castration-resistant disease.