Molecular oncology, 2013-06, Vol.7 (3), p.484-496
2013
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Details
- Autor(en) / Beteiligte
- Titel
- Glioma pathogenesis-related protein 1 induces prostate cancer cell death through Hsc70-mediated suppression of AURKA and TPX2
- Ist Teil von
- Molecular oncology, 2013-06, Vol.7 (3), p.484-496
- Ort / Verlag
- United States: Elsevier B.V
- Erscheinungsjahr
- 2013
- Quelle
- Wiley Online Library - AutoHoldings Journals
- Beschreibungen/Notizen
- 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. ► GLIPR1 inhibits AURKA and TPX2 and induces apoptosis and/or MC in human PCa cells. ► GLIPR1 interacts with Hsc70, leading to destabilization of SP1 and c-Myb. ► Inhibition of SP1 or c-Myb leads to suppression of AURKA and TPX2 transcription. ► Recombinant GLIPR1-ΔTM protein suppresses orthotopic xenograft tumor growth.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1574-7891eISSN: 1878-0261DOI: 10.1016/j.molonc.2012.12.005Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3907183
- Format
- –
- Schlagworte
- Androgens, Apoptosis, AURKA, Aurora Kinase A - genetics, c-Myb, Cancer therapies, Cell cycle, Cell Cycle Proteins - genetics, Cell Cycle Proteins - metabolism, Cell Death, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Gene Knockdown Techniques, Genes, Glioma, Glioma pathogenesis-related protein 1 (GLIPR1), Heat shock proteins, Hsc70, HSC70 Heat-Shock Proteins - genetics, HSC70 Heat-Shock Proteins - metabolism, Hsc70 protein, Humans, Kinases, Male, Medical research, Membrane Proteins, Metastases, Microtubule-Associated Proteins - genetics, Microtubule-Associated Proteins - metabolism, Neoplasm Proteins - genetics, Neoplasm Proteins - metabolism, Nerve Tissue Proteins - genetics, Nerve Tissue Proteins - metabolism, Nuclear Proteins - genetics, Nuclear Proteins - metabolism, p53 Protein, Pathogenesis, Phosphatase, Prostate - metabolism, Prostate - pathology, Prostate cancer, Prostatic Neoplasms - genetics, Prostatic Neoplasms - metabolism, Prostatic Neoplasms - pathology, Protein Interaction Maps, Proteins, Proto-Oncogene Proteins c-myb - genetics, Proto-Oncogene Proteins c-myb - metabolism, Signal transduction, siRNA, Sp1 protein, TPX2, Transcription, Tumors, Up-Regulation, Xenografts