Please use this identifier to cite or link to this item: https://doi.org/10.18632/oncotarget.2730
Title: Overexpression of N-terminal kinase like gene promotes tumorigenicity of hepatocellular carcinoma by regulating cell cycle progression and cell motility
Authors: Wang, J
Liu, M
Chen, L 
Chan, T.H.M 
Jiang, L
Yuan, Y.-F
Guan, X.-Y
Keywords: agar
cyclin D1
dynamin II
F actin
guanosine triphosphatase
n terminal kinase like protein
protein
protein Cdc42
protein p53
Rac1 protein
unclassified drug
CHD1L protein, human
DNA binding protein
DNA helicase
DNM2 protein, human
dynamin
SCYL1 protein, human
transcription factor
adult
amino terminal kinase like gene
animal cell
animal experiment
animal model
animal tissue
apoptosis
Article
cancer prognosis
carcinogenesis
carcinogenicity
cell cycle progression
cell division
cell growth
cell motility
CHD1L oncogene
chromatin immunoprecipitation
chromosome segregation
colony formation
controlled study
correlation analysis
cytokinesis
enzyme phosphorylation
female
G1 phase cell cycle checkpoint
gene
gene expression
gene overexpression
human
human tissue
lamellipodium
liver cell carcinoma
major clinical study
male
mass spectrometry
mitosis
mouse
mutation
nonhuman
nude mouse
oncogene
phenotype
promoter region
real time polymerase chain reaction
animal
biosynthesis
cell cycle
cell motion
cell proliferation
enzymology
genetics
liver cell carcinoma
liver tumor
metabolism
middle aged
pathology
physiology
tumor cell line
xenograft
Animals
Apoptosis
Carcinoma, Hepatocellular
Cell Cycle
Cell Line, Tumor
Cell Movement
Cell Proliferation
DNA Helicases
DNA-Binding Proteins
Dynamins
Female
Gene Expression
Heterografts
Humans
Liver Neoplasms
Male
Mice
Middle Aged
Transcription Factors
Issue Date: 2015
Citation: Wang, J, Liu, M, Chen, L, Chan, T.H.M, Jiang, L, Yuan, Y.-F, Guan, X.-Y (2015). Overexpression of N-terminal kinase like gene promotes tumorigenicity of hepatocellular carcinoma by regulating cell cycle progression and cell motility. Oncotarget 6 (3) : 1618-1630. ScholarBank@NUS Repository. https://doi.org/10.18632/oncotarget.2730
Rights: Attribution 4.0 International
Abstract: Amplification and overexpression of CHD1L is one of the most frequent genetic alterations in hepatocellular carcinoma (HCC). Here we found that one of CHD1L downstream targets, NTKL, was frequently upregulated in HCC, which was significantly correlated with vascular invasion (P = 0.012) and poor prognosis (P = 0.050) of HCC. ChIP assay demonstrated the binding of CHD1L to the promoter region of NTKL. QRT-PCR study showed that the expression of NTKL positively correlated with CHD1L expression in both clinical samples and cell lines. Functional study found that NTKL had strong oncogenic roles, including increased cell growth, colony formation in soft agar, and tumor formation in nude mice. Further study found that NTKL could promote G1/S transition by decreasing P53 and increasing CyclinD1 expressions. NTKL overexpression could accelerate the mitotic exit and chromosome segregation, which led to the cytokinesis failure and subsequently induced apoptosis. NTKL also regulated cell motility by facilitating philopodia and lamellipodia formation through regulating F-actin reorganization and the phosphorylation of small GTPase Rac1/ cdc42. Using co-IP and mass spectrometry approach, we identified the large GTPase dynamin2 as an interacting protein of NTKL, which might be responsible for the phenotype alterations caused by NTKL overexpression, such as cytokinesis failure, increased cell motility and abnormal of cell division.
Source Title: Oncotarget
URI: https://scholarbank.nus.edu.sg/handle/10635/180963
ISSN: 19492553
DOI: 10.18632/oncotarget.2730
Rights: Attribution 4.0 International
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