title: Glioma pathogenesis-related protein 1 induces prostate cancer cell death through Hsc70-mediated suppression of AURKA and TPX2.
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.
authors: Department of Genitourinary Medical Oncology, Unit 18-3, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
authors: Likun
authors: L
authors: Li
authors: Guang
authors: G
authors: Yang
authors: Chengzhen
authors: C
authors: Ren
authors: Ryuta
authors: R
authors: Tanimoto
authors: Takahiro
authors: T
authors: Hirayama
authors: Jianxiang
authors: J
authors: Wang
authors: David
authors: D
authors: Hawke
authors: Soo Mi
authors: SM
authors: Kim
authors: Ju-Seog
authors: JS
authors: Lee
authors: Alexei A
authors: AA
authors: Goltsov
authors: Sanghee
authors: S
authors: Park
authors: Michael M
authors: MM
authors: Ittmann
authors: Patricia
authors: P
authors: Troncoso
authors: Timothy C
authors: TC
authors: Thompson
mesh_terms: D017209:Apoptosis; D064096:Aurora Kinase A / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D016923:Cell Death; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D050883:HSC70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011467:Prostate / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D060066:Protein Interaction Maps; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D018797:Cell Cycle Proteins; C094538:GLIPR1 protein, human; D050883:HSC70 Heat-Shock Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D020598:Proto-Oncogene Proteins c-myb; C122167:TPX2 protein, human; D064096:Aurora Kinase A