title: GSK-3β-regulated N-acetyltransferase 10 is involved in colorectal cancer invasion.
abstract: OBJECTIVE
  NAT10 (N-acetyltransferase 10) is a nucleolar protein, but may show subcellular redistribution in colorectal carcinoma. In this study, we evaluated membranous staining of NAT10 in colorectal carcinoma and its clinical implications, and explored the mechanism of regulation of NAT10 redistribution.
  
  
  METHODS
  The expression and subcellular redistribution of NAT10, β-catenin, E-cadherin, and GSK-3β were evaluated by immunohistochemistry in 222 cases of colorectal carcinoma. Regulation of NAT10 and its influence on cell motility were analyzed with inhibitors of GSK-3β, transfection of wild-type or kinase-inactivated GSK-3β, or expression of various domains of NAT10, and evaluated with immunofluorescence, Western blotting, and Transwell assays.
  
  
  RESULTS
  NAT10 localized mainly in the nucleoli of normal tissues, and was redistributed to the membrane in cancer cells, particularly at the invasive "leading edge" of the tumor. This correlated well with nuclear accumulation of β-catenin (P<0.001; χ2=68.213). In addition, NAT10 membrane staining reflected the depth of invasion and tendency to metastasize (all P values<0.001), and was associated with a poorer prognosis (P=0.023; χ2=5.161). Evaluation of the mechanism involved demonstrated that subcellular redistribution of NAT10 may result from its increased stability and nuclear export, which is brought about by inhibition of GSK-3β. Moreover, redistribution of NAT10 induces alteration of cytoskeletal dynamics and increases cancer cell motility.
  
  
  CONCLUSIONS
  The subcellular redistribution of NAT10 can be induced by decreases in GSK-3β activity. This redistribution increases cancer cell motility, and is, thus, correlated with invasive potential and poorer clinical outcome. This finding suggests that NAT10 may be a useful prognostic marker and potential therapeutic target in colorectal carcinoma.
authors: Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors: Hong
authors: H
authors: Zhang
authors: Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors: Wei
authors: W
authors: Hou
authors: Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors: Hua-Li
authors: HL
authors: Wang
authors: Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors: Hai-Jing
authors: HJ
authors: Liu
authors: Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors: Xin-Ying
authors: XY
authors: Jia
authors: Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors: Xing-Zheng
authors: XZ
authors: Zheng
authors: Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors: Yong-Xin
authors: YX
authors: Zou
authors: Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors: Xin
authors: X
authors: Li
authors: Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors: Lin
authors: L
authors: Hou
authors: Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors: Michael A
authors: MA
authors: McNutt
authors: Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China. zhangbo@bjmu.edu.cn.
authors: Bo
authors: B
authors: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000096:biosynthesis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008297:Male; D008875:Middle Aged; D063213:N-Terminal Acetyltransferase E / Q000096:biosynthesis* / Q000235:genetics; D063206:N-Terminal Acetyltransferases; D009361:Neoplasm Invasiveness / Q000235:genetics; D051176:beta Catenin / Q000096:biosynthesis
chemical_list: D015820:Cadherins; D051176:beta Catenin; D063213:N-Terminal Acetyltransferase E; D063206:N-Terminal Acetyltransferases; C522989:NAT10 protein, human; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3