title: Tumour-suppressive function of SIRT4 in human colorectal cancer.
abstract: BACKGROUND
  SIRT4, which is localised in the mitochondria, is one of the least characterised members of the sirtuin family of nicotinamide adenine dinucleotide-dependent enzymes that play key roles in multiple cellular processes such as metabolism, stress response and longevity. There are only a few studies that have characterised its function and assessed its clinical significance in human cancers.
  
  
  METHODS
  We established colorectal cancer cell lines (SW480, HCT116, and HT29) overexpressing SIRT4 and investigated their effects on proliferation, migration and invasion, as well as E-cadherin expression, that negatively regulates tumour invasion and metastases. The associations between SIRT4 expression in colorectal cancer specimens and clinicopathological features including prognosis were assessed by immunohistochemistry.
  
  
  RESULTS
  SIRT4 upregulated E-cadherin expression and suppressed proliferation, migration and invasion through inhibition of glutamine metabolism in colorectal cancer cells. Moreover, SIRT4 expression in colorectal cancer decreased with the progression of invasion and metastasis, and a low expression level of SIRT4 was correlated with a worse prognosis.
  
  
  CONCLUSIONS
  SIRT4 has a tumour-suppressive function and may serve as a novel therapeutic target in colorectal cancer.
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Miyo
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Konno
authors.affiliation: 1] Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan [2] Department of Cancer Profiling Discovery, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Colvin
authors.affiliation: Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Nishida
authors.affiliation: Department of Cancer Profiling Discovery, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Koseki
authors.affiliation: 1] Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan [2] Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kawamoto
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ogawa
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Hamabe
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Uemura
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Nishimura
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hata
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Takemasa
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Mizushima
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Doki
authors.affiliation: Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Mori
authors.affiliation: 1] Department of Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan [2] Department of Cancer Profiling Discovery, Osaka University Graduate School of Medicine, Yamadaoka 2-2, Suita, Osaka 565-0871, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Ishii
mesh_terms: D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D016147:Genes, Tumor Suppressor; D005973:Glutamine / Q000378:metabolism; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D024101:Mitochondrial Proteins / Q000502:physiology*; D009361:Neoplasm Invasiveness; D011379:Prognosis; D037761:Sirtuins / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: D024101:Mitochondrial Proteins; D005973:Glutamine; C525357:SIRT4 protein, human; D037761:Sirtuins