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.
Written by:
Li L, Yang G, Ren C, Tanimoto R, Hirayama T, Wang J, Hawke D, Kim SM, Lee JS, Goltsov AA, Park S, Ittmann MM, Troncoso P, Thompson TC. Are you the author?
Department of Genitourinary Medical Oncology, Unit 18-3, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030-4009, USA
Reference: Mol Oncol. 2012 Dec 31. pii: S1574-7891(12)00131-7 (Epub ahead of print)
doi: 10.1016/j.molonc.2012.12.005
PubMed Abstract
PMID: 23333597
