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Androgen receptor-interacting protein HSPBAP1 facilitates growth of prostate cancer cells in androgen-deficient

Khalid Saeed1, Päivi Östling, Mari Björkman

  • 1Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki, Finland.

International Journal of Cancer
|November 1, 2014
PubMed

Insights

Heat shock 27 kDa-associated protein 1 (HSPBAP1) helps prostate cancer cells survive androgen deprivation by maintaining androgen receptor (AR) signaling. Inhibiting HSPBAP1 may synergize with androgen deprivation therapy for advanced prostate cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Hormonal therapies targeting the androgen receptor (AR) are crucial for prostate cancer (PCa) treatment.
  • PCa often progresses to fatal castrate-resistant disease despite hormonal therapy.
  • Understanding cellular survival pathways during androgen deprivation is key to improving treatment efficacy.

Purpose of the Study:

  • To identify novel survival and stress pathways involved in PCa progression during androgen deprivation.
  • To find potential therapeutic targets that can synergize with androgen deprivation therapy.

Main Methods:

  • Conducted an RNAi screen of 2,068 genes in VCaP cells under androgen-deprived conditions.
  • Utilized high-content cell spot microarray (CSMA) with Ki67 and cleaved ADP-ribose polymerase (cPARP) assays.
  • Confirmed candidate gene expression and protein localization via immunohistochemistry (IHC) and chromatin immunoprecipitation (ChIP).

Main Results:

  • Identified 39 candidate genes that, when silenced, inhibited proliferation or induced apoptosis under androgen deprivation.
  • HSPBAP1 (heat shock 27 kDa-associated protein 1) was a key candidate, highly expressed in tumors and correlated with higher Gleason grade.
  • Strong HSPBAP1 IHC staining predicted shorter disease-specific survival in PCa patients.
  • Demonstrated HSPBAP1 interacts with AR in the nucleus during androgen deprivation and regulates AR target gene enhancers (PSA/klk3, TMPRSS2/tmprss2).

Conclusions:

  • HSPBAP1 plays a critical role in maintaining prostate cancer cell viability under androgen-deprived conditions.
  • HSPBAP1 sustains AR signaling, suggesting it as a potential therapeutic target to overcome resistance to androgen deprivation therapy.
Keywords:
HSPBAP1RNAi sensitizationandrogen receptorcell spot microarray (CSMA)prostate cancer

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