Angiogenin mediates androgen-stimulated prostate cancer growth and enables castration resistance

Shuping Li, Miaofen G. Hu, Yeqing Sun, Norie Yoshioka, Soichiro Ibaragi, Jinghao Sheng, Guangjie Sun, Koji Kishimoto, Guo Fu Hu

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

The androgen receptor (AR) is a critical effector of prostate cancer development and progression. Androgendependent prostate cancer is reliant on the function of AR for growth and progression. Most castration-resistant prostate cancer (CRPC) remains dependent on AR signaling for survival and growth. Ribosomal RNA (rRNA) is essential for both androgen-dependent and castration-resistant growth of prostate cancer cells. During androgendependent growth of prostate cells, androgen-AR signaling leads to the accumulation of rRNA. However, the mechanism by which AR regulates rRNA transcription is unknown. Here, investigation revealed that angiogenin (ANG), a member of the secreted ribonuclease superfamily, is upregulated in prostate cancer and mediates androgen-stimulated rRNA transcription in prostate cancer cells. Upon androgen stimulation, ANG undergoes nuclear translocation in androgen-dependent prostate cancer cells, where it binds to the rDNA promoter and stimulates rRNA transcription. ANG antagonists inhibit androgen-induced rRNA transcription and cell proliferation in androgen-dependent prostate cancer cells. Interestingly, ANG also mediates androgen-independent rRNA transcription through a mechanism that involves its constitutive nuclear translocation in androgeninsensitive prostate cancer cells, resulting in a constant rRNA overproduction and thereby stimulating cell proliferation. Critically, ANG overexpression in androgen-dependent prostate cancer cells enables castrationresistant growth of otherwise androgen-dependent cells. Thus, ANG-stimulated rRNA transcription is not only an essential component for androgen-dependent growth of prostate cancer but also contributes to the transition of prostate cancer from androgen-dependent to castration-resistant growth status. Implications: The ability of angiogenin to regulate rRNA transcription and prostate cancer growth makes it a viable target for therapy.

Original languageEnglish
Pages (from-to)1203-1214
Number of pages12
JournalMolecular Cancer Research
Volume11
Issue number10
DOIs
Publication statusPublished - Oct 2013

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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