title: Transmembrane protease serine 4 promotes thyroid cancer proliferation via CREB phosphorylation.
abstract: BACKGROUND
  Transmembrane protease serine 4 (TMPRSS4), one of the type II transmembrane serine proteases (TTSPs), is elevated in various cancers and is associated with multiple malignant phenotypes. However, the expression pattern and biologic significance of TMPRSS4 in thyroid cancer are largely unknown. In this study, we investigated the expression of TMPRSS4 in thyroid cancer and assessed the pro-proliferative role of TMPRSS4 in thyroid cancer.
  
  
  METHODS
  Immunohistochemistry and real-time reverse transcription-polymerase chain reaction (RT-PCR) assays were performed to assess the expression of TMPRSS4 in thyroid cancer. We evaluated in vitro cell proliferation using MTT, colony formation, anchorage-independent growth, flow cytometry analysis, and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assays. Western blot, real-time RT-PCR, and luciferase assays were conducted to reveal the underlying mechanisms.
  
  
  RESULTS
  TMPRSS4 is overexpressed in thyroid cancer and is associated with the grade of malignancy. Depletion of TMPRSS4 in thyroid cancer cells significantly suppressed proliferation. Moreover, the proliferation of thyroid cancer cells with TMPRSS4 overexpression was significantly enhanced. We also show that cyclic adenosine monophosphate response element-binding protein (CREB)-cyclin D1 signaling mediates, at least partially, the role of TMPRSS4 in thyroid cancer cell proliferation.
  
  
  CONCLUSIONS
  TMPRSS4 is overexpressed in thyroid cancer and TMPRSS4-CREB signaling is needed to sustain thyroid cancer cell proliferation.
authors.affiliation: Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-sen University , Guangzhou, Guangdong, China .
authors.forename: Hongyu
authors.initials: H
authors.lastname: Guan
authors.forename: Weiwei
authors.initials: W
authors.lastname: Liang
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.forename: Guohong
authors.initials: G
authors.lastname: Wei
authors.forename: Hai
authors.initials: H
authors.lastname: Li
authors.forename: Lingling
authors.initials: L
authors.lastname: Xiu
authors.forename: Haipeng
authors.initials: H
authors.lastname: Xiao
authors.forename: Yanbing
authors.initials: Y
authors.lastname: Li
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002291:Carcinoma, Papillary / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D060787:Neoplasm Grading; D010766:Phosphorylation; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D017362:Cyclic AMP Response Element-Binding Protein; D008565:Membrane Proteins; D012697:Serine Endopeptidases; C528837:TMPRSS4 protein, human