title: PID1 (NYGGF4), a new growth-inhibitory gene in embryonal brain tumors and gliomas.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Authors' Affiliations: Departments of Pediatrics, Pathology, Radiology, and Neurosurgery, at the Saban Research Institute at Children's Hospital Los Angeles, Norris Comprehensive Cancer Center; Departments of Preventive Medicine and Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California; Division of Pediatric Neurooncology at the German Cancer Research Center DKFZ; and Department of Pediatric Hematology and Oncology, Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Anat
authors.initials: A
authors.lastname: Erdreich-Epstein
authors.forename: Nathan
authors.initials: N
authors.lastname: Robison
authors.forename: Xiuhai
authors.initials: X
authors.lastname: Ren
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.forename: Jingying
authors.initials: J
authors.lastname: Xu
authors.forename: Tom B
authors.initials: TB
authors.lastname: Davidson
authors.forename: Mathew
authors.initials: M
authors.lastname: Schur
authors.forename: Floyd H
authors.initials: FH
authors.lastname: Gilles
authors.forename: Lingyun
authors.initials: L
authors.lastname: Ji
authors.forename: Jemily
authors.initials: J
authors.lastname: Malvar
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Shackleford
authors.forename: Ashley S
authors.initials: AS
authors.lastname: Margol
authors.forename: Mark D
authors.initials: MD
authors.lastname: Krieger
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Judkins
authors.forename: David T W
authors.initials: DT
authors.lastname: Jones
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Pfister
authors.forename: Marcel
authors.initials: M
authors.lastname: Kool
authors.forename: Richard
authors.initials: R
authors.lastname: Sposto
authors.forename: Shahab
authors.initials: S
authors.lastname: Asgharzadeh
authors.forename: Shahab
authors.initials: S
authors.lastname: Asgharazadeh
mesh_terms: D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002528:Cerebellar Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008527:Medulloblastoma / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C514653:PID1 protein, human; D012333:RNA, Messenger