title: GLI pathogenesis-related 1 functions as a tumor-suppressor in lung cancer.
abstract: BACKGROUND
  GLI pathogenesis-related 1 (GLIPR1) was originally identified in glioblastomas and its expression was also found to be down-regulated in prostate cancer. Functional studies revealed both growth suppression and proapoptotic activities for GLIPR1 in multiple cancer cell lines. GLIPR1's role in lung cancer has not been investigated. Protein arginine methyltransferase 5 (PRMT5) is a protein arginine methyltransferase and forms a stoichiometric complex with the WD repeat domain 77 (WDR77) protein. Both PRMT5 and WDR77 are essential for growth of lung epithelial and cancer cells. But additional gene products that interact genetically or biochemichally with PRMT5 and WDR77 in the control of lung cancer cell growth are not characterized.
  
  
  METHODS
  DNA microarray and immunostaining were used to detect GLIPR1 expression during lung development and lung tumorigenesis. GLIPR1 expression was also analyzed in the TCGA lung cancer cohort. The consequence of GLIPR1 on growth of lung cancer cells in the tissue culture and lung tumor xenografts in the nude mice was observed.
  
  
  RESULTS
  We found that GLIPR1 expression is negatively associated with PRMT5/WDR77. GLIPR1 is absent in growing epithelial cells at the early stages of mouse lung development and highly expressed in the adult lung. Expression of GLIPR1 was down-regulated during lung tumorigenesis and its expression suppressed growth of lung cancer cells in the tissue culture and lung tumor xenografts in mice. GLIPR1 regulates lung cancer growth through the V-Erb-B avian erythroblastic leukemia viral oncogene homolog 3 (ErbB3).
  
  
  CONCLUSIONS
  This study reveals a novel pathway that PRMT5/WDR77 regulates GLIPR1 expression to control lung cancer cell growth and GLIPR1 as a potential therapeutic agent for lung cancer.
authors.affiliation: School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, 212013, China.|The Center for Cancer Research and Therapeutic Development, Department of Biological Sciences, Clark Atlanta University, 223 James P. Brawley Drive, S.W., Atlanta, Georgia, 30314, USA.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Sheng
authors.affiliation: The Center for Cancer Research and Therapeutic Development, Department of Biological Sciences, Clark Atlanta University, 223 James P. Brawley Drive, S.W., Atlanta, Georgia, 30314, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: Bowen
authors.affiliation: The Center for Cancer Research and Therapeutic Development, Department of Biological Sciences, Clark Atlanta University, 223 James P. Brawley Drive, S.W., Atlanta, Georgia, 30314, USA. zwang@cau.edu.
authors.forename: Zhengxin
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation / Q000235:genetics; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D059565:G2 Phase Cell Cycle Checkpoints / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008168:Lung / Q000196:embryology / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D008565:Membrane Proteins; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D020893:Receptor, ErbB-3 / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C094538:GLIPR1 protein, human; C478359:WDR77 protein, human
keywords: ErbB3; GLIPR1; Lung; Lung cancer; PRMT5; Tumor suppressor; WDR77