title: Overexpression of N-terminal kinase like gene promotes tumorigenicity of hepatocellular carcinoma by regulating cell cycle progression and cell motility.
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.
authors.affiliation: Departments of Clinical Oncology, The University of Hong Kong, Hong Kong, China.|State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China.|Center for Cancer Research, The University of Hong Kong, Hong Kong, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: Departments of Clinical Oncology, The University of Hong Kong, Hong Kong, China.|State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China.|Center for Cancer Research, The University of Hong Kong, Hong Kong, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.affiliation: Departments of Clinical Oncology, The University of Hong Kong, Hong Kong, China.|State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China.
authors.forename: Leilei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Departments of Clinical Oncology, The University of Hong Kong, Hong Kong, China.|State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China.
authors.forename: Tim Hon Man
authors.initials: TH
authors.lastname: Chan
authors.affiliation: Departments of Clinical Oncology, The University of Hong Kong, Hong Kong, China.|State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China.
authors.forename: Lingxi
authors.initials: L
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Yuan
authors.affiliation: Departments of Clinical Oncology, The University of Hong Kong, Hong Kong, China.|State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China.|Center for Cancer Research, The University of Hong Kong, Hong Kong, China.|State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Guan
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D034285:Dynamin II; D034281:Dynamins / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D064593:Heterografts; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D004268:DNA-Binding Proteins; C464929:SCYL1 protein, human; D014157:Transcription Factors; D004265:DNA Helicases; C543585:CHD1L protein, human; C000593490:DNM2 protein, human; D034285:Dynamin II; D034281:Dynamins