title: A vicious partnership between AKT and PHLDA3 to facilitate neuroendocrine tumors.
abstract: Pancreatic neuroendocrine tumors (PanNET) are rare cancers that generally have a poor prognosis. Accurate diagnosis and proper treatment of these tumors requires a better understanding of the molecular mechanisms underlying the development of PanNET. It has been shown that the mTOR inhibitor everolimus can improve the progression-free survival of PanNET patients, suggesting that inhibition of the PI3K-Akt-mTOR pathway may suppress the progression of PanNET. PHLDA3 is a novel tumor suppressor protein that inhibits Akt activation by competition for binding to PIP3. Our analysis of PanNET revealed frequent loss-of-heterozygosity and DNA methylation at the PHLDA3 locus, resulting in strong suppression of PHLDA3 transcription. Such alterations in the PHLDA3 gene were also frequently found in lung neuroendocrine tumors (NET), suggesting the possibility that various types of NET have in common the functional loss of the PHLDA3 gene.
authors.affiliation: Division of Rare Cancer Research, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takikawa
authors.affiliation: Division of Rare Cancer Research, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Rieko
authors.identifier: http://orcid.org/0000-0002-7775-6653
authors.initials: R
authors.lastname: Ohki
mesh_terms: D000818:Animals; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology; D018358:Neuroendocrine Tumors / Q000235:genetics* / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D009687:Nuclear Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: 
  AKT
  ; PHLDA3; PanNET; neuroendocrine tumors; p53