Prostate cancer cells incubated with CM from P4+TFE3+ CAF exhibited a significant increase in 3D sphere formation under 10 μm ENZ compared to controls (Figure4A,B), indicative of enhanced tumor‐initiating capacity. Consistent with the role of cancer stem‐like cells (CSCs) in therapeutic resistance via lineage plasticity and survival adaptation.[21, 22] In accordance with this observation, the protein levels of SOX2, BMI1, CD133, TWIST1, and SLUG, which are indicative of stemness activity, were found to be increased in P4+TFE3+ CAF cultured prostate tumor cells (Figure 4C). This evidence concerns the gene SOX2 and prostate neoplasm.