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PID1 (NYGGF4), a new growth-inhibitory gene in embryonal brain tumors and gliomas.

AbstractPURPOSE:
We present here the first report of PID1 (Phosphotyrosine Interaction Domain containing 1; NYGGF4) in cancer. PID1 was identified in 2006 as a gene that modulates insulin signaling and mitochondrial function in adipocytes and muscle cells.
EXPERIMENTAL DESIGN AND RESULTS:
Using four independent medulloblastoma datasets, we show that mean PID1 mRNA levels were lower in unfavorable medulloblastomas (groups 3 and 4, and anaplastic histology) compared with favorable medulloblastomas (SHH and WNT groups, and desmoplastic/nodular histology) and with fetal cerebellum. In two large independent glioma datasets, PID1 mRNA was lower in glioblastomas (GBM), the most malignant gliomas, compared with other astrocytomas, oligodendrogliomas and nontumor brains. Neural and proneural GBM subtypes had higher PID1 mRNA compared with classical and mesenchymal GBM. Importantly, overall survival and radiation-free progression-free survival were longer in medulloblastoma patients whose tumors had higher PID1 mRNA (univariate and multivariate analyses). Higher PID1 mRNA also correlated with longer overall survival in patients with glioma and GBM. In cell culture, overexpression of PID1 inhibited colony formation in medulloblastoma, atypical teratoid rhabdoid tumor (ATRT), and GBM cell lines. Increasing PID1 also increased cell death and apoptosis, inhibited proliferation, induced mitochondrial depolaization, and decreased serum-mediated phosphorylation of AKT and ERK in medulloblastoma, ATRT, and/or GBM cell lines, whereas siRNA to PID1 diminished mitochondrial depolarization.
CONCLUSIONS:
These data are the first to link PID1 to cancer and suggest that PID1 may have a tumor inhibitory function in these pediatric and adult brain tumors.
AuthorsAnat Erdreich-Epstein, Nathan Robison, Xiuhai Ren, Hong Zhou, Jingying Xu, Tom B Davidson, Mathew Schur, Floyd H Gilles, Lingyun Ji, Jemily Malvar, Gregory M Shackleford, Ashley S Margol, Mark D Krieger, Alexander R Judkins, David T W Jones, Stefan M Pfister, Marcel Kool, Richard Sposto, Shahab Asgharzadeh, Shahab Asgharazadeh
JournalClinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 20 Issue 4 Pg. 827-36 (Feb 15 2014) ISSN: 1557-3265 [Electronic] United States
PMID24300787 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Copyright©2013 AACR
Chemical References
  • Carrier Proteins
  • PID1 protein, human
  • RNA, Messenger
Topics
  • Carrier Proteins (genetics, metabolism)
  • Cell Line, Tumor
  • Cerebellar Neoplasms (genetics, metabolism, mortality)
  • Child, Preschool
  • Disease-Free Survival
  • Female
  • Gene Expression
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Medulloblastoma (genetics, metabolism, mortality)
  • Neoplasms, Germ Cell and Embryonal (genetics, metabolism, mortality)
  • Proportional Hazards Models
  • RNA, Messenger (genetics, metabolism)

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