title: PTPRZ1 regulates calmodulin phosphorylation and tumor progression in small-cell lung carcinoma.
abstract: BACKGROUND
  Small-cell lung carcinoma (SCLC) is a neuroendocrine tumor subtype and comprises approximately 15% of lung cancers. Because SCLC is still a disease with a poor prognosis and limited treatment options, there is an urgent need to develop targeted molecular agents for this disease.
  
  
  METHODS
  We screened 20 cell lines from a variety of pathological phenotypes established from different organs by RT-PCR. Paraffin-embedded tissue from 252 primary tumors was examined for PTPRZ1 expression using immunohistochemistry. shRNA mediated PTPRZ1 down-regulation was used to study impact on tyrosine phosphorylation and in vivo tumor progression in SCLC cell lines.
  
  
  RESULTS
  Here we show that PTPRZ1, a member of the protein tyrosine- phosphatase receptor (PTPR) family, is highly expressed in SCLC cell lines and specifically exists in human neuroendocrine tumor (NET) tissues. We also demonstrate that binding of the ligand of PTPRZ1, pleiotrophin (PTN), activates the PTN/PTPRZ1 signaling pathway to induce tyrosine phosphorylation of calmodulin (CaM) in SCLC cells, suggesting that PTPRZ1 is a regulator of tyrosine phosphorylation in SCLC cells. Furthermore, we found that PTPRZ1 actually has an important oncogenic role in tumor progression in the murine xenograft model.
  
  
  CONCLUSIONS
  PTPRZ1 was highly expressed in human NET tissues and PTPRZ1 is an oncogenic tyrosine phosphatase in SCLCs. These results imply that a new signaling pathway involving PTPRZ1 could be a feasible target for treatment of NETs.
authors.affiliation: Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Makinoshima
authors.forename: Genichiro
authors.initials: G
authors.lastname: Ishii
authors.forename: Motohiro
authors.initials: M
authors.lastname: Kojima
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fujii
authors.forename: Youichi
authors.initials: Y
authors.lastname: Higuchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kuwata
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ochiai
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002147:Calmodulin / Q000378:metabolism*; D018278:Carcinoma, Neuroendocrine / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation / Q000502:physiology; D011379:Prognosis; D034741:RNA, Small Interfering / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5 / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055752:Small Cell Lung Carcinoma / Q000235:genetics / Q000378:metabolism*
chemical_list: D002147:Calmodulin; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D020794:Receptor Protein-Tyrosine Kinases; C516895:PTPRZ1 protein, human; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5