We developed a mouse model with prostate-specific Lkb1 knockout in a Pten-null background, performed histological examination and scRNA-seq analyses, and found that LKB1 loss not only promoted prostate cancer aggressiveness but also facilitated AR-independent lineage transition, consistent with a previous study.33 This lineage transition, driven by LKB1 loss, was characterized by a significant decrease in AR and its target genes, alongside castration resistance. This evidence concerns the gene PTEN and prostate carcinoma.