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

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

Molecular oncology (2013-01-22)
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
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Myb Antibody, clone 1-1, clone 1-1, Upstate®, from mouse
Sigma-Aldrich
Anti-acetyl-Histone H3 (Lys27) Antibody, serum, Upstate®
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Anti-trimethyl-Histone H3 (Lys27) Antibody, Upstate®, from rabbit
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Anti-Aurora-A Kinase antibody, Mouse monoclonal, clone 35C1, purified from hybridoma cell culture
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Anti-β-Actin antibody, Mouse monoclonal, clone AC-15, purified from hybridoma cell culture