An IKKAα-E2F1-BMI1 cascade activated by infiltrating B cells controls prostate regeneration and tumor recurrence

Massimo Ammirante, Ali I. Kuraishy, Shabnam Shalapour, Amy Strasner, Claudia Ramirez-Sanchez, Weizhou Zhang, Ahmed Shabaik, Michael Karin

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

Androgen-deprived prostate cancer (PCa) is infiltrated by B lymphocytes that produce cytokines that activate IkB kinase a (IKKa) to accelerate the emergence of castrationresistant tumors. We now demonstrate that infiltrating B lymphocytes and IKKa are also required for androgendependent expansion of epithelial progenitors responsible for prostate regeneration. In these cells and in PCa cells, IKKa 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 IKKa-BMI1 pathway is also activated in human PCa.

Original languageEnglish
Pages (from-to)1435-1440
Number of pages6
JournalGenes and Development
Volume27
Issue number13
DOIs
StatePublished - 1 Jul 2013
Externally publishedYes

Keywords

  • B cells
  • Prostate
  • Regeneration

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