title: SETDB1 accelerates tumourigenesis by regulating the WNT signalling pathway.
abstract: We investigated the oncogenic role of SETDB1, focusing on non-small cell lung cancer (NSCLC), which has high expression of this protein. A total of 387 lung cancer cases were examined by immunohistochemistry; 72% of NSCLC samples were positive for SETDB1 staining, compared to 46% samples of normal bronchial epithelium (106 cases) (p <0.0001). The percentage of positive cells and the intensity of staining increased significantly with increased grade of disease. Forced expression of SETDB1 in NSCLC cell lines enhanced their clonogenic growth in vitro and markedly increased tumour size in a murine xenograft model, while silencing (shRNA) SETDB1 in NSCLC cells slowed their proliferation. SETDB1 positively stimulated activity of the WNT-β-catenin pathway and diminished P53 expression, resulting in enhanced NSCLC growth in vitro and in vivo. Our finding suggests that therapeutic targeting of SETDB1 may benefit patients whose tumours express high levels of SETDB1.
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore.
authors.forename: Qiao-Yang
authors.initials: QY
authors.lastname: Sun
authors.forename: Ling-Wen
authors.initials: LW
authors.lastname: Ding
authors.forename: Jin-Fen
authors.initials: JF
authors.lastname: Xiao
authors.forename: Wenwen
authors.initials: W
authors.lastname: Chien
authors.forename: Su-Lin
authors.initials: SL
authors.lastname: Lim
authors.forename: Norimichi
authors.initials: N
authors.lastname: Hattori
authors.forename: Lee
authors.initials: L
authors.lastname: Goodglick
authors.forename: David
authors.initials: D
authors.lastname: Chia
authors.forename: Vei
authors.initials: V
authors.lastname: Mah
authors.forename: Mohammad
authors.initials: M
authors.lastname: Alavi
authors.forename: Sara R
authors.initials: SR
authors.lastname: Kim
authors.forename: Ngan B
authors.initials: NB
authors.lastname: Doan
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Said
authors.forename: Xin-Yi
authors.initials: XY
authors.lastname: Loh
authors.forename: Liang
authors.initials: L
authors.lastname: Xu
authors.forename: Li-Zhen
authors.initials: LZ
authors.lastname: Liu
authors.forename: Henry
authors.initials: H
authors.lastname: Yang
authors.forename: Takahide
authors.initials: T
authors.lastname: Hayano
authors.forename: Shuo
authors.initials: S
authors.lastname: Shi
authors.forename: Dong
authors.initials: D
authors.lastname: Xie
authors.forename: De-Chen
authors.initials: DC
authors.lastname: Lin
authors.forename: H Phillip
authors.initials: HP
authors.lastname: Koeffler
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D008819:Mice, Nude; D060787:Neoplasm Grading; D009368:Neoplasm Transplantation; D011496:Protein Methyltransferases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C454062:SETDB1 protein, human
keywords: SETDB1; WNT; lung; tumourigenesis