title: Signal Peptide Peptidase, Encoded by HM13, Contributes to Tumor Progression by Affecting EGFRvIII Secretion Profiles in Glioblastoma.
abstract: OBJECTIVE
  EGFRvIII is the most prevalent glioblastoma mutation, occurring in more than 25% of glioblastomas. EGFRvIII cells release microvesicles that contain proteins, miRNAs, and mRNAs that enhance the growth and survival of surrounding tumor cells. However, little is known about the maturation process and regulatory mechanisms of secreted vesicles in EGFRvIII cells.
  
  
  METHODS
  Signal peptide peptidase (SPP) provides a fascinating mechanism for protein cleavage and subsequent dislocation in the endoplasmic reticulum transmembrane domain.
  
  
  RESULTS
  In this study, we reported that SPP facilitates the secretion of cytokines in vitro and promotes tumor progression in mice. Human cytokine antibody arrays revealed that EGFRvIII secreted higher levels of cytokines, but these levels were significantly reduced following SPP knockdown, suggesting that cytokines in EGFRvIII secretion profiles play important roles in GBM development. Identical results were confirmed in intracellular maturation tracking of TGF-β1 in mouse serum. Clinically, analyses of GBM patient data from the database revealed that HM13 expression was closely related to patient prognosis and survival, suggesting an influence by the secreted vesicles of EGFRvIII tumor cells.
  
  
  CONCLUSIONS
  Collectively, our study identifies that SPP affects EGFRvIII secretion profiles and thus promotes tumor progression, providing further understanding of the formation of secreted vesicles and driving role of EGFRvIII in GBM.
authors.affiliation: Department of Neurosurgery, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Key Laboratory of Post-Neuro injury Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Jian-Wei
authors.initials: JW
authors.lastname: Wei
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, NanGang District, Harbin, Heilongjiang Province, China.
authors.forename: Jin-Quan
authors.initials: JQ
authors.lastname: Cai
authors.affiliation: Department of Neurosurgery, The Hospital affiliated to Hebei University, Baoding, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Fang
authors.affiliation: College of Fundamental Medicine, Hebei University, Baoding, China.
authors.forename: Yan-Li
authors.initials: YL
authors.lastname: Tan
authors.affiliation: Department of Neurosurgery, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Key Laboratory of Post-Neuro injury Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Huang
authors.affiliation: Department of Neurosurgery, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Key Laboratory of Post-Neuro injury Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, NanGang District, Harbin, Heilongjiang Province, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, NanGang District, Harbin, Heilongjiang Province, China.
authors.forename: Chuan-Lu
authors.initials: CL
authors.lastname: Jiang
authors.affiliation: Department of Neurosurgery, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Key Laboratory of Post-Neuro injury Neuro-repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Chun-Sheng
authors.initials: CS
authors.lastname: Kang
mesh_terms: D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism*; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009154:Mutation / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000097:blood / Q000378:metabolism
chemical_list: D016207:Cytokines; D034741:RNA, Small Interfering; D016211:Transforming Growth Factor alpha; D053773:Transforming Growth Factor beta1; C410723:epidermal growth factor receptor VIII; D066246:ErbB Receptors; D016282:Aspartic Acid Endopeptidases; C460085:signal peptide peptidase
keywords: 
  SPP
  ; EGFRvIII; Glioblastoma; Secreted vesicles; TGF-β1