title: SOX2 oncogenes amplified and operate to activate AKT signaling in gastric cancer and predict immunotherapy responsiveness.
abstract: BACKGROUND
  Gastric cancer is the second leading cause of cancer mortality in the world. Whether the oncogene, amplified on chromosome 3q26, SOX2, a master transcriptional regulator of stemness, operate to drive strong growth phenotype in gastric cancer were unknown.
  
  
  METHODS
  The gene expression changes of SOX2 in human gastric cancer tissues compared with non-cancerous tissues was detected using real-time quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) analysis and immunohistochemistry, which identified the gene overexpression of SOX2 in gastric cancer. Moreover, we discovered that SOX2 promoted cancer cell proliferation in vitro/vivo and SOX2 expression correlated with elevated AKT phosphorylation in gastric cancer, while the AKT phosphorylation was required for SOX2's oncogenic effects. Next, our data point to the usefulness of SOX2 overexpression, as a new predictive marker for responsiveness to trastuzumab.
  
  
  CONCLUSIONS
  SOX2 is a commonly activated tumor promoter that activate AKT signaling in gastric cancer and a new predictive marker for targeted therapy.
authors.affiliation: Hangzhou Sanatorium Health Management Center, Hangzhou, 310007, People's Republic of China.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Tian
authors.forename: Xin
authors.initials: X
authors.lastname: Jia
authors.forename: Shengxiang
authors.initials: S
authors.lastname: Wang
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Li
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.forename: Da
authors.initials: D
authors.lastname: Cai
authors.forename: Zequan
authors.initials: Z
authors.lastname: Zhou
authors.forename: Junmin
authors.initials: J
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Luo
authors.forename: Maosheng
authors.initials: M
authors.lastname: Dong
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D011379:Prognosis; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D051058:Oncogene Protein v-akt
references.citation: Stem Cells. 2013 Dec;31(12):2632-46
references.pmid: 23963638
references.citation: Cancer Res. 2006 Feb 1;66(3):1630-9
references.pmid: 16452222
references.citation: Cancer Chemother Pharmacol. 2007 May;59(6):795-805
references.pmid: 17031648
references.citation: Nature. 2003 Feb 13;421(6924):756-60
references.pmid: 12610629
references.citation: Int J Cancer. 2002 Jun 20;99(6):783-91
references.pmid: 12115478
references.citation: Oncogene. 2003 May 22;22(21):3205-12
references.pmid: 12761490
references.citation: J Clin Oncol. 2006 May 10;24(14):2137-50
references.pmid: 16682732
references.citation: Cancer Cell. 2002 Aug;2(2):127-37
references.pmid: 12204533
references.citation: PLoS One. 2010 Feb 09;5(2):e9112
references.pmid: 20161759
references.citation: N Engl J Med. 2006 Dec 28;355(26):2733-43
references.pmid: 17192538
references.citation: J Natl Cancer Inst. 2000 Feb 2;92(3):205-16
references.pmid: 10655437
references.citation: Am J Respir Cell Mol Biol. 2011 Jul;45(1):101-10
references.pmid: 20855650
references.citation: Lancet. 2012 Jan 28;379(9813):315-21
references.pmid: 22226517
references.citation: J Natl Cancer Inst. 2001 Dec 19;93(24):1852-7
references.pmid: 11752009
references.citation: Lancet. 2010 Aug 28;376(9742):687-97
references.pmid: 20728210
references.citation: Oncogene. 1996 Jul 4;13(1):63-72
references.pmid: 8700555
references.citation: J Natl Cancer Inst. 2007 Apr 18;99(8):628-38
references.pmid: 17440164
references.citation: PLoS One. 2010 Jan 29;5(1):e8960
references.pmid: 20126410
references.citation: Cancer Cell. 2004 Nov;6(5):459-69
references.pmid: 15542430
references.citation: Cytometry A. 2004 Feb;57(2):86-93
references.pmid: 14750129
references.citation: Int J Cancer. 2010 Dec 15;127(12):2893-917
references.pmid: 21351269
references.citation: Cancer Cell. 2004 Apr;5(4):317-28
references.pmid: 15093539
references.citation: Cancer Res. 1990 May 1;50(9):2773-80
references.pmid: 2158397
references.citation: Mod Pathol. 2001 Mar;14(3):213-8
references.pmid: 11266529
references.citation: Nat Genet. 2009 Nov;41(11):1238-42
references.pmid: 19801978
references.citation: Int J Oncol. 2008 Jan;32(1):89-95
references.pmid: 18097546
references.citation: N Engl J Med. 2005 Oct 20;353(16):1652-4
references.pmid: 16236735
references.citation: Cancer Res. 2005 Jan 15;65(2):473-82
references.pmid: 15695389
references.citation: PLoS One. 2009 Dec 14;4(12):e8248
references.pmid: 20011520
references.citation: Oncogene. 2012 Apr 12;31(15):1869-83
references.pmid: 21892204
references.citation: JAMA. 2010 May 5;303(17):1729-37
references.pmid: 20442389
references.citation: CA Cancer J Clin. 2008 May-Jun;58(3):130-60
references.pmid: 18322143
references.citation: Mol Cell Biol. 1999 Oct;19(10):6845-57
references.pmid: 10490623