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

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.
Mesh Terms:
Apoptosis, Aurora Kinase A, Cell Cycle Proteins, Cell Death, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Gene Knockdown Techniques, HSC70 Heat-Shock Proteins, Humans, Male, Microtubule-Associated Proteins, Neoplasm Proteins, Nerve Tissue Proteins, Nuclear Proteins, Prostate, Prostatic Neoplasms, Protein Interaction Maps, Proto-Oncogene Proteins c-myb, Up-Regulation
Mol Oncol
Date: Jun. 01, 2013
Download Curated Data For This Publication
204283
Switch View:
  • Interactions 10