Glioma pathogenesis-related protein 1 induces prostate cancer cell death through Hsc70-mediated suppression of AURKA and TPX2

Likun Li, Guang Yang, Chengzhen Ren, Ryuta Tanimoto, Takahiro Hirayama, Jianxiang Wang, David Hawke, Soo Mi Kim, Ju Seog Lee, Alexei A. Goltsov, Sanghee Park, Michael M. Ittmann, Patricia Troncoso, Timothy C. Thompson

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

In this study we report that expression of glioma pathogenesis-related protein 1 (GLIPR1) regulated numerous apoptotic, cell cycle, and spindle/centrosome assembly-related genes, including AURKA and TPX2, and induced apoptosis and/or mitotic catastrophe (MC) in prostate cancer (PCa) cells, including p53-mutated/deleted, androgen-insensitive metastatic PCa cells. Mechanistically, GLIPR1 interacts with heat shock cognate protein 70 (Hsc70); this interaction is associated with SP1 and c-Myb destabilization and suppression of SP1- and c-Myb-mediated AURKA and TPX2 transcription. Inhibition of AURKA and TPX2 using siRNA mimicked enforced GLIPR1 expression in the induction of apoptosis and MC. Recombinant GLIPR1-ΔTM protein inhibited AURKA and TPX2 expression, induced apoptosis and MC, and suppressed orthotopic xenograft tumor growth. Our results define a novel GLIPR1-regulated signaling pathway that controls apoptosis and/or mitotic catastrophe in PCa cells and establishes the potential of this pathway for targeted therapies.

Original languageEnglish
Pages (from-to)484-496
Number of pages13
JournalMolecular Oncology
Volume7
Issue number3
DOIs
Publication statusPublished - Jun 2013

Keywords

  • AURKA
  • C-Myb
  • Glioma pathogenesis-related protein 1 (GLIPR1)
  • Hsc70
  • Prostate cancer
  • TPX2

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Oncology
  • Cancer Research

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  • Cite this

    Li, L., Yang, G., Ren, C., Tanimoto, R., Hirayama, T., Wang, J., Hawke, D., Kim, S. M., Lee, J. S., Goltsov, A. A., Park, S., Ittmann, M. M., Troncoso, P., & Thompson, T. C. (2013). Glioma pathogenesis-related protein 1 induces prostate cancer cell death through Hsc70-mediated suppression of AURKA and TPX2. Molecular Oncology, 7(3), 484-496. https://doi.org/10.1016/j.molonc.2012.12.005