Glioma pathogenesis‐related protein 1 induces prostate cancer cell death through Hsc70‐mediated suppression of AURKA and TPX2
Copyright policy )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.
- Baylor College of Medicine United States
- The University of Texas MD Anderson Cancer Center United States
- Jeonbuk National University Korea (Republic of)
Male, Cell Death, HSC70 Heat-Shock Proteins, Prostate, Membrane Proteins, Nuclear Proteins, Prostatic Neoplasms, Apoptosis, Cell Cycle Proteins, Nerve Tissue Proteins, Neoplasm Proteins, Up-Regulation, Gene Expression Regulation, Neoplastic, Proto-Oncogene Proteins c-myb, Cell Line, Tumor, Gene Knockdown Techniques, Humans, Protein Interaction Maps, Microtubule-Associated Proteins, Aurora Kinase A
Male, Cell Death, HSC70 Heat-Shock Proteins, Prostate, Membrane Proteins, Nuclear Proteins, Prostatic Neoplasms, Apoptosis, Cell Cycle Proteins, Nerve Tissue Proteins, Neoplasm Proteins, Up-Regulation, Gene Expression Regulation, Neoplastic, Proto-Oncogene Proteins c-myb, Cell Line, Tumor, Gene Knockdown Techniques, Humans, Protein Interaction Maps, Microtubule-Associated Proteins, Aurora Kinase A
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