Zinc finger protein 191 inhibits hepatocellular carcinoma metastasis through discs large 1-mediated yes-associated protein inactivation

Di Wu, Guoyuan Liu, Yufeng Liu, Hexige Saiyin, Chenji Wang, Zhen Wei, Wenjiao Zen, Danyang Liu, Qi Chen, Zhonghua Zhao, Liping Zou, Haojie Huang, Songmin Jiang, Long Yu

Research output: Contribution to journalArticle

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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. 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.

Original languageEnglish (US)
JournalHepatology
DOIs
StateAccepted/In press - 2016

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Zinc Fingers
Hepatocellular Carcinoma
Neoplasm Metastasis
Proteins
Cell Movement
Cell Polarity
Chromatin Immunoprecipitation
Protein Transport

ASJC Scopus subject areas

  • Hepatology

Cite this

Zinc finger protein 191 inhibits hepatocellular carcinoma metastasis through discs large 1-mediated yes-associated protein inactivation. / 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.

In: Hepatology, 2016.

Research output: Contribution to journalArticle

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. / Zinc finger protein 191 inhibits hepatocellular carcinoma metastasis through discs large 1-mediated yes-associated protein inactivation. In: Hepatology. 2016.
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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. 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.",
author = "Di Wu and Guoyuan Liu and Yufeng Liu and Hexige Saiyin and Chenji Wang and Zhen Wei and Wenjiao Zen and Danyang Liu and Qi Chen and Zhonghua Zhao and Liping Zou and Haojie Huang and Songmin Jiang and Long Yu",
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AU - Wu, Di

AU - Liu, Guoyuan

AU - Liu, Yufeng

AU - Saiyin, Hexige

AU - Wang, Chenji

AU - Wei, Zhen

AU - Zen, Wenjiao

AU - Liu, Danyang

AU - Chen, Qi

AU - Zhao, Zhonghua

AU - Zou, Liping

AU - Huang, Haojie

AU - Jiang, Songmin

AU - Yu, Long

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

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