Premium
Zinc finger protein 191 inhibits hepatocellular carcinoma metastasis through discs large 1‐mediated yes‐associated protein inactivation
Author(s) -
Wu Di,
Liu Guoyuan,
Liu Yufeng,
Saiyin Hexige,
Wang Chenji,
Wei Zhen,
Zen Wenjiao,
Liu Danyang,
Chen Qi,
Zhao Zhonghua,
Zou Liping,
Huang Haojie,
Jiang Songmin,
Yu Long
Publication year - 2016
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.28708
Subject(s) - metastasis suppressor , biology , cancer research , metastasis , zinc finger , chromatin immunoprecipitation , microbiology and biotechnology , cell polarity , crosstalk , cell migration , gene knockdown , cell growth , cell , cell culture , promoter , transcription factor , genetics , gene , gene expression , cancer , physics , optics
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. Conclusion: 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 . (H epatology 2016;64:1148‐1162)