Polydopamine-Coated Surfaces Promote Adhesion, Migration, Proliferation, Chemoresistance, Stemness, and Epithelial–Mesenchymal Transition of Human Prostate Cancer Cell Lines In Vitro via Integrin α2β1–FAK–JNK Signaling

Polydopamine (PDA) surface coatings are widely used in biomedical engineering to enhance cell-substrate interactions; however, their effects on cancer-cell behavior remain unclear. In this study, we investigated how PDA-coated two-dimensional (2D) culture surfaces influence oncogenic traits of human prostate cancer (PC) cells in vitro. Using LNCaP, DU145, and PC3 cell lines, we found that PDA-coated substrates markedly increased the adhesion, migration, invasion, proliferation, and colony formation in a dose- and time-dependent manner. PDA exposure also induced epithelial-mesenchymal transition (EMT), upregulated cancer stem cell markers (<i>CD44</i>, <i>CD117</i>, <i>CD133</i>, <i>Sox2</i>, <i>Oct4</i>, and <i>Nanog</i>), and elevated expression of metastasis- and chemoresistance-associated molecules (<i>MMP-2</i>, <i>MMP-9</i>, <i>MDR1</i>, and <i>MRP1</i>). Mechanistically, PDA coatings enhanced integrin α₂β₁-associated cell adhesion, accompanied by increased focal adhesion kinase (FAK) phosphorylation and downstream activation of JNK signaling. Pharmacological inhibition of integrin α₂β₁ (BTT-3033), FAK (PF573228) and JNK (SP600125) effectively abrogated PDA-induced malignant phenotypes and restored chemosensitivity to cabazitaxel, cisplatin, docetaxel, curcumin, and enzalutamide. Collectively, these findings identify PDA-coated surfaces as a simple, efficient, and reductionist in vitro platform for studying adhesion-mediated signaling and phenotypic plasticity in PC cells, while acknowledging that further validation in three-dimensional (3D) and patient-derived models will be required to establish in vivo relevance.