SCGB1A1 suppresses prostate cancer proliferation and metastasis by modulating the MAPK signaling pathway

Prostate cancer represents a prevalent urological malignancy, but the molecular mechanisms underlying the differentiation of distinct tumor cell subtypes have not been fully elucidated.

We conducted an analysis of paired single-cell RNA sequencing data from the public database on prostate cancer, and discovered differentially expressed genes between tumor cells and normal epithelial cells. We evaluated the expression of SCGB1A1 in prostate cell lines and tissue samples, and assessed migration, invasion, and proliferation through CCK-8, EdU, wound healing, and Transwell experiments. We performed pathway enrichment analysis to explore the downstream mechanism of SCGB1A1 (Secretoglobin Family 1A Member 1).

Single-cell transcriptomic analysis revealed a marked reduction in SCGB1A1⁺ epithelial cells within tumor tissues, accompanied by an increased abundance of KLK3⁺ tumor epithelial cells. SCGB1A1 expression was significantly downregulated in both prostate cancer cell lines and tumor epithelial cells. Functional assays demonstrated that SCGB1A1 overexpression suppressed the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of prostate cancer cells. SCGB1A1 expression is negatively correlated with the activation of the MAPK signaling pathway, which may be associated with its tumor-suppressive effects.

Our findings identify SCGB1A1 as a previously underappreciated tumor-suppressive role in prostate cancer and reveal its role in modulating MAPK signaling and EMT. The depletion of SCGB1A1⁺ epithelial cells characterizes the malignant epithelial phenotype, suggesting its potential as a candidate diagnostic biomarker and therapeutic target that requires further clinical validation.