RT Journal Article
SR Electronic
T1 ZNF191 Inhibits Hepatocellular Carcinoma Metastasis via DLG1-mediated YAP1 Inactivation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 027060
DO 10.1101/027060
A1 Di Wu
A1 Haitao Li
A1 Yufeng Liu
A1 Hexige Saiyin
A1 Chenji Wang
A1 Zhen Wei
A1 Wenjiao Zen
A1 Danyang Liu
A1 Qi Chen
A1 Haojie Huang
A1 Guoyuan Liu
A1 Songmin Jiang
A1 Long Yu
YR 2015
UL http://biorxiv.org/content/early/2015/09/18/027060.abstract
AB Searching targets for hepatocellular carcinoma (HCC) treatment, we identified zinc finger protein 191 (ZNF191) as a suppressor against HCC metastasis. Over-expressing ZNF191 in HCC cells impaired cell motility, while ZNF191 depletion promoted HCC cell migration in vitro and metastasis in vivo through triggering yes-associated protein 1 (YAP1) signaling. Chromatin immunoprecipitation-sequencing (ChIP-seq) revealed that ZNF191 specifically bound to the promoter of Discs, Large homolog 1 (DLG1), a cell polarity maintainer and a negative regulator of YAP1. Double-knockdown experiments showed that DLG1 was not only the mediator of ZNF191’s function to suppress migration but also a link between ZNF191 and YAP1 signaling. ZNF191 was down-regulated in metastatic HCCs, correlating positively with DLG1 levels and inversely with YAP1 activation. Our findings indicate ZNF191 functions as a metastasis suppressor via DLG1-mediated YAP1 signaling inactivation.