title: PICT1 regulates TP53 via RPL11 and is involved in gastric cancer progression.
abstract: BACKGROUND
  The TP53 pathway is frequently inactivated in human cancers. PICT1 (also known as GLTSCR2) is a novel regulator of the MDM2-TP53 pathway via its interaction with the ribosomal protein RPL11 in the nucleolus. However, the clinical significance of PICT1 in gastric cancer remains unknown.
  
  
  METHODS
  To evaluate PICT1 function, we used shRNA to inhibit PICT1 expression in gastric cancer cells that expressed wild-type TP53. PICT1 expression and TP53 mutation status were quantified in 110 cases of primary gastric cancer to explore the impact of PICT1 expression levels on gastric cancer.
  
  
  RESULTS
  Deficiency of PICT1 significantly impaired cell proliferation and colony formation via TP53-mediated cell cycle arrest. Following induction of PICT1 deficiency, RPL11 translocated out of the nucleolus. Of the 110 gastric cancer samples tested, 70 (63.6%) and 40 (36.4%) tumours expressed wild-type and mutant TP53, respectively. In gastric cancer patients with wild-type TP53 tumours, patients with relatively low PICT1 expression levels had a better prognosis compared with high expression level patients (P=0.046).
  
  
  CONCLUSIONS
  The findings suggest that PICT1 has a crucial role in gastric cancer progression by regulating the MDM2-TP53 pathway through RPL11. Clinically, PICT1 expression is a novel prognostic parameter in gastric cancer patients with wild-type TP53 tumours.
authors.affiliation: 1] Department of Surgery, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu 874-0838, Japan [2] Department of Otorhinolaryngology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Uchi
authors.forename: R
authors.initials: R
authors.lastname: Kogo
authors.forename: K
authors.initials: K
authors.lastname: Kawahara
authors.forename: T
authors.initials: T
authors.lastname: Sudo
authors.forename: T
authors.initials: T
authors.lastname: Yokobori
authors.forename: H
authors.initials: H
authors.lastname: Eguchi
authors.forename: K
authors.initials: K
authors.lastname: Sugimachi
authors.forename: T
authors.initials: T
authors.lastname: Maehama
authors.forename: M
authors.initials: M
authors.lastname: Mori
authors.forename: A
authors.initials: A
authors.lastname: Suzuki
authors.forename: S
authors.initials: S
authors.lastname: Komune
authors.forename: K
authors.initials: K
authors.lastname: Mimori
mesh_terms: D002466:Cell Nucleolus / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
chemical_list: C500712:NOP53 protein, human; D012269:Ribosomal Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C027624:ribosomal protein L11; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2
references.citation: J Biol Chem. 2004 Oct 29;279(44):45300-3
references.pmid: 15355975
references.citation: Nature. 2012 Mar 28;483(7391):603-7
references.pmid: 22460905
references.citation: Mol Cell. 2010 Oct 22;40(2):216-27
references.pmid: 20965417
references.citation: Anal Biochem. 2005 Jan 1;336(1):138-40
references.pmid: 15582570
references.citation: J Natl Cancer Inst. 1998 Oct 7;90(19):1473-9
references.pmid: 9776413
references.citation: Gastroenterology. 2010 Oct;139(4):1333-43
references.pmid: 20547161
references.citation: Nucleic Acids Res. 2011 Jan;39(Database issue):D691-7
references.pmid: 21067998
references.citation: Oncogene. 1999 Jul 15;18(28):4144-52
references.pmid: 10435596
references.citation: Cancer Res. 2008 Jul 15;68(14):5760-8
references.pmid: 18632629
references.citation: Mol Cell. 2009 Aug 14;35(3):316-26
references.pmid: 19683495
references.citation: Mol Biol Cell. 2006 Nov;17(11):4888-95
references.pmid: 16971513
references.citation: Nature. 1997 May 15;387(6630):299-303
references.pmid: 9153396
references.citation: J Clin Oncol. 2006 Oct 10;24(29):4758-63
references.pmid: 16966689
references.citation: J Biol Chem. 2008 May 2;283(18):12387-92
references.pmid: 18305114
references.citation: Nat Rev Cancer. 2006 Dec;6(12):909-23
references.pmid: 17128209
references.citation: Nat Med. 2011 Jul 31;17(8):944-51
references.pmid: 21804542
references.citation: Mol Cell Biol. 2000 Nov;20(21):8185-97
references.pmid: 11027288
references.citation: Mol Cell Biol. 2005 Jul;25(13):5389-95
references.pmid: 15964796
references.citation: Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
references.pmid: 16199517
references.citation: Cancer Res. 2009 May 1;69(9):3788-94
references.pmid: 19366810
references.citation: Cell. 1993 Nov 19;75(4):817-25
references.pmid: 8242752
references.citation: Cell. 1995 Jan 27;80(2):293-9
references.pmid: 7834749
references.citation: Hum Mutat. 2003 Mar;21(3):258-70
references.pmid: 12619111
references.citation: Cell Death Differ. 2007 Nov;14(11):1872-9
references.pmid: 17657248
references.citation: Nature. 1997 May 15;387(6630):296-9
references.pmid: 9153395