title: GADD34 Promotes Tumor Growth by Inducing Myeloid-derived Suppressor Cells.
abstract: Tumor hypoxia induces the expression of growth arrest and DNA damage-inducible protein (GADD34). However, the role of GADD34 in tumor growth remains unclear.
  
  
  
  Gadd34 expression was knocked-down through lentivirus-mediated short hairpin RNA (shRNA) in tumor cells, which were subsequently injected subcutaneously into mice. Tumor volumes and myeloid-derived suppressor cells (MDSCs) were monitored. Isolated MDSCs were incubated with tumor supernatant to investigate the impact of GADD34 on cytokine secretion of MDSCs.
  
  
  
  We observed that reduction of GADD34 expression significantly suppressed tumor, and resulted in decreased accumulation of MDSCs and T-cells, and inhibition of GADD34 reduced secretion of vascular epithelial growth factor α and transforming growth factor β by MDSCs.
  
  
  
  These findings provide a promising strategy for targeting GADD34 activity in order to inhibit tumor growth.
authors.affiliation: Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan Liulintao2013@Gmail.com.
authors.forename: Lintao
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Ito
authors.affiliation: Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Nishio
authors.affiliation: Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Tanaka
authors.affiliation: Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Isobe
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D018827:Carcinoma, Lewis Lung / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000737:chemistry; D004249:DNA Damage; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D000860:Hypoxia; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D022423:Myeloid Cells / Q000166:cytology*; D000072737:Myeloid-Derived Suppressor Cells / Q000166:cytology*; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D054645:Protein Phosphatase 1 / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D017077:Culture Media, Conditioned; D034741:RNA, Small Interfering; D016212:Transforming Growth Factor beta; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C087519:PPP1R15A protein, human; D054645:Protein Phosphatase 1
keywords: GADD34; Gr1+CD11b+ MDSC; Lewis lung carcinoma; TGFβ; VEGFA