An IKKα–E2F1–BMI1 Cascade Activated by Infiltrating B Cells Controls Prostate Regeneration and Tumor Recurrence

“Androgen-deprived prostate cancer (PCa) is infiltrated by B lymphocytes that produce cytokines that activate IκB kinase α (IKKα) to accelerate the emergence of castration-resistant tumors. We now demonstrate that infiltrating B lymphocytes and IKKα are also required for androgen-dependent expansion of epithelial progenitors responsible for prostate regeneration. In these cells and in PCa cells, IKKα phosphorylates transcription factor E2F1 on a site that promotes its nuclear translocation, association with the coactivator CBP, and recruitment to critical genomic targets that include Bmi1, a key regulator of normal and cancerous prostate stem cell renewal. The IKKα–BMI1 pathway is also activated in human PCa.”

The Pivotal Role of IKKα in the Development of Spontaneous Lung Squamous Cell Carcinomas

Here, we report that kinase-dead IKKα knockin mice develop spontaneous lung squamous cell carcinomas (SCCs) associated with IKKα downregulation and marked pulmonary inflammation…”