Cancer-Associated Fibroblast-Derived CCL11 Promotes Prostate Cancer Malignancy by Inducing Epithelial-Mesenchymal Transition via CDK5

To elucidate the key role and underlying mechanisms of C-C motif chemokine ligand 11 (CCL11) in cancer-associated fibroblasts (CAFs)-mediated prostate cancer (PCa) progression. In this study, we analyzed the dataset GSE85606 and validated the upregulation of CCL11 in CAFs using ELISA and qRT-PCR, demonstrating its strong correlation with established CAF biomarkers. Using CAFs-conditioned medium, recombinant human CCL11, specific siRNA, and CDK5 plasmid or siRNA in PCa cell lines (C42 and 22RV1), we investigated the functional role of CCL11. RNA-seq and TCGA database analyses predicted a CCL11’s downstream target (CDK5). Transwell, wound healing, and flow cytometry assays, along with Western blot, were employed to assess the effects of CCL11 on migration, invasion, apoptosis, and epithelial-mesenchymal transition (EMT) pathways. The results indicate that CCL11, predominantly secreted by PCa-derived CAFs, significantly enhances the migration and invasion of PCa cells, suppresses their apoptosis, and activates the EMT pathway, largely through regulating CDK5 expression. Collectively, our findings suggest that CAFs-derived CCL11 may represent a potential therapeutic target for PCa.