This research article examines how Pten deletion triggers the transformation of adult prostate basal cells into multi-lineage stem cells, leading to the initiation of invasive tumors. Through techniques like single-cell RNA sequencing, the authors discovered that this cellular plasticity occurs primarily in specific prostate regions and is driven by the activation of innate immunity and the NF-κB signaling pathway. The study highlights that the cell of origin significantly dictates how aggressive a tumor becomes, noting that cancers derived from basal cells often exhibit more inflammation and stromal infiltration than those from luminal cells. Genetic experiments further show that combining Pten loss with other mutations, such as Pik3ca or p53, dramatically accelerates the reprogramming process. Ultimately, the findings suggest that using pharmacological inhibitors to target these inflammatory pathways could provide new strategies for the prevention and treatment of prostate cancer.

References:

• Jiang C, Song Y, Rorive S, et al. Innate immunity and the NF-κB pathway control prostate stem cell plasticity, reprogramming and tumor initiation[J]. Nature Cancer, 2025, 6(9): 1537-1558.