title: Zinc finger protein 191 inhibits hepatocellular carcinoma metastasis through discs large 1-mediated yes-associated protein inactivation.
abstract: Interplay between cell polarity module Scribble-Lethal Giant Larvae-Discs Large 1 (DLG1) and Yes-associated protein (YAP) appears critical in tumor metastasis. We identified zinc finger protein 191 (ZNF191) as a metastasis suppressor acting through DLG-YAP crosstalk in hepatocellular carcinoma (HCC). Overexpression of ZNF191 in HCC cells impaired cell motility, while ZNF191 depletion promoted cell migration in vitro and metastasis in vivo through triggering YAP signaling. Chromatin immunoprecipitation-sequencing revealed that ZNF191 specifically bound to the promoter of DLG1, a cell polarity maintainer and a negative regulator of YAP. The binding sequence of ZNF191 at the DLG1 promoter is a seven-repeat of TCAT motif. Double-knockdown experiments inferred that DLG1 was not only the mediator of the function of ZNF191 to suppress migration but also a link between ZNF191 and YAP signaling. Decreased expression of ZNF191 in human metastatic HCC specimens correlated positively with DLG1 levels but inversely with YAP activation. Our findings illustrate a YAP-targeting, antimetastasis function of ZNF191, thereby representing a possible prognostic marker and a potential target for metastasis therapy.
  
  
  
  ZNF191 directly binds to the DLG1 promoter at a typical TCAT repeating motif and activates the expression of DLG1; through up-regulating DLG1, ZNF191 inhibits cell migration and YAP activation in HCC cells and eventually inhibits metastasis. (Hepatology 2016;64:1148-1162).
authors.affiliation: State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, PR China.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, PR China. gyliu@fudan.edu.cn.
authors.forename: Guoyuan
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, PR China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, PR China.
authors.forename: Hexige
authors.initials: H
authors.lastname: Saiyin
authors.affiliation: State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, PR China.
authors.forename: Chenji
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, PR China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wei
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, PR China.
authors.forename: Wenjiao
authors.initials: W
authors.lastname: Zen
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, PR China.
authors.forename: Danyang
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, PR China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, PR China.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Huashan Hospital, Fudan University, Shanghai, PR China.
authors.forename: Liping
authors.initials: L
authors.lastname: Zou
authors.affiliation: Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Rochester, MN. huang.haojie@mayo.edu.
authors.forename: Haojie
authors.initials: H
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, PR China. smjiang@fudan.edu.cn.
authors.forename: Songmin
authors.initials: S
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, PR China. longyu@fudan.edu.cn.
authors.forename: Long
authors.initials: L
authors.lastname: Yu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000556:secondary*; D002352:Carrier Proteins / Q000502:physiology*; D018797:Cell Cycle Proteins; D002465:Cell Movement; D000074288:Discs Large Homolog 1 Protein; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000502:physiology*; D010750:Phosphoproteins / Q000502:physiology*; D000074407:SAP90-PSD95 Associated Proteins; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D000074288:Discs Large Homolog 1 Protein; C000614189:Dlg1 protein, mouse; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D000074407:SAP90-PSD95 Associated Proteins; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse; C474810:Zfp24 protein, mouse