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

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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. © 2012 Federation of European Biochemical Societies.

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Li, L., Yang, G., Ren, C., Tanimoto, R., Hirayama, T., Wang, J., … 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

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