Yes-associated protein is required for zo-1-mediated tight-junction integrity and cell migration in e-cadherin-restored ags gastric cancer cells

Seon Young Kim; Song Yi Park; Hwan Seok Jang; Yong Doo Park; Sun-Ho Kee

doi:10.3390/biomedicines9091264

Yes-associated protein is required for zo-1-mediated tight-junction integrity and cell migration in e-cadherin-restored ags gastric cancer cells

Seon Young Kim, Song Yi Park, Hwan Seok Jang, Yong Doo Park, Sun-Ho Kee

Department of Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

Abstract

Yes-associated protein (YAP) regulates numerous cellular homeostasis processes and malignant transformation. We found that YAP influences ZO-1-mediated cell migration using E-cadherin-restored EC96 cells derived from gastric malignant AGS cells. Ectopic expression of E-cadherin enhanced straightforward migration of cells, in comparison to the meandering movement of parental AGS cells. In EC96 cells, YAP and ZO-1 expression increased but nuclear YAP levels and activity were reduced. Nuclear factor-κB (NF-κB) mediated the increase in ZO-1 expression, possibly stabilizing cytoplasmic YAP post-translationally. Downregulation of YAP expression using siYAP RNA or stable knock-down inhibited straightforward cell migration by fragmenting ZO-1 containing tight junctions (TJs) but not adherens junctions, implying involvement of YAP in ZO-1-mediated cell migration. The association of YAP with ZO-1 was mediated by angiomotin (AMOT) because downregulation of AMOT dissociated YAP from ZO-1 and reduced cell migration. E-cadherin restoration in malignant cancer cells induced NF-κB signaling to enhance ZO-1 expression and subsequently stabilize YAP. At high expression levels, YAP associates with ZO-1 via AMOT at TJs, influencing ZO-1-mediated cell migration and maintaining TJ integrity.

Original language	English
Article number	1264
Journal	Biomedicines
Volume	9
Issue number	9
DOIs	https://doi.org/10.3390/biomedicines9091264
Publication status	Published - 2021 Sept

Bibliographical note

Funding Information:
Funding: This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (No. NRF-2019R1F1A1058999).

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

Angiomotin
Cell migration
E-cadherin
Tight junction
YAP
ZO-1

ASJC Scopus subject areas

Medicine (miscellaneous)
Biochemistry, Genetics and Molecular Biology(all)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/biomedicines9091264

Cite this

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title = "Yes-associated protein is required for zo-1-mediated tight-junction integrity and cell migration in e-cadherin-restored ags gastric cancer cells",

abstract = "Yes-associated protein (YAP) regulates numerous cellular homeostasis processes and malignant transformation. We found that YAP influences ZO-1-mediated cell migration using E-cadherin-restored EC96 cells derived from gastric malignant AGS cells. Ectopic expression of E-cadherin enhanced straightforward migration of cells, in comparison to the meandering movement of parental AGS cells. In EC96 cells, YAP and ZO-1 expression increased but nuclear YAP levels and activity were reduced. Nuclear factor-κB (NF-κB) mediated the increase in ZO-1 expression, possibly stabilizing cytoplasmic YAP post-translationally. Downregulation of YAP expression using siYAP RNA or stable knock-down inhibited straightforward cell migration by fragmenting ZO-1 containing tight junctions (TJs) but not adherens junctions, implying involvement of YAP in ZO-1-mediated cell migration. The association of YAP with ZO-1 was mediated by angiomotin (AMOT) because downregulation of AMOT dissociated YAP from ZO-1 and reduced cell migration. E-cadherin restoration in malignant cancer cells induced NF-κB signaling to enhance ZO-1 expression and subsequently stabilize YAP. At high expression levels, YAP associates with ZO-1 via AMOT at TJs, influencing ZO-1-mediated cell migration and maintaining TJ integrity.",

keywords = "Angiomotin, Cell migration, E-cadherin, Tight junction, YAP, ZO-1",

author = "Kim, {Seon Young} and Park, {Song Yi} and Jang, {Hwan Seok} and Park, {Yong Doo} and Sun-Ho Kee",

note = "Funding Information: Funding: This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (No. NRF-2019R1F1A1058999). Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

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AU - Kim, Seon Young

AU - Park, Song Yi

AU - Jang, Hwan Seok

AU - Park, Yong Doo

AU - Kee, Sun-Ho

N1 - Funding Information: Funding: This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (No. NRF-2019R1F1A1058999). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/9

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N2 - Yes-associated protein (YAP) regulates numerous cellular homeostasis processes and malignant transformation. We found that YAP influences ZO-1-mediated cell migration using E-cadherin-restored EC96 cells derived from gastric malignant AGS cells. Ectopic expression of E-cadherin enhanced straightforward migration of cells, in comparison to the meandering movement of parental AGS cells. In EC96 cells, YAP and ZO-1 expression increased but nuclear YAP levels and activity were reduced. Nuclear factor-κB (NF-κB) mediated the increase in ZO-1 expression, possibly stabilizing cytoplasmic YAP post-translationally. Downregulation of YAP expression using siYAP RNA or stable knock-down inhibited straightforward cell migration by fragmenting ZO-1 containing tight junctions (TJs) but not adherens junctions, implying involvement of YAP in ZO-1-mediated cell migration. The association of YAP with ZO-1 was mediated by angiomotin (AMOT) because downregulation of AMOT dissociated YAP from ZO-1 and reduced cell migration. E-cadherin restoration in malignant cancer cells induced NF-κB signaling to enhance ZO-1 expression and subsequently stabilize YAP. At high expression levels, YAP associates with ZO-1 via AMOT at TJs, influencing ZO-1-mediated cell migration and maintaining TJ integrity.

AB - Yes-associated protein (YAP) regulates numerous cellular homeostasis processes and malignant transformation. We found that YAP influences ZO-1-mediated cell migration using E-cadherin-restored EC96 cells derived from gastric malignant AGS cells. Ectopic expression of E-cadherin enhanced straightforward migration of cells, in comparison to the meandering movement of parental AGS cells. In EC96 cells, YAP and ZO-1 expression increased but nuclear YAP levels and activity were reduced. Nuclear factor-κB (NF-κB) mediated the increase in ZO-1 expression, possibly stabilizing cytoplasmic YAP post-translationally. Downregulation of YAP expression using siYAP RNA or stable knock-down inhibited straightforward cell migration by fragmenting ZO-1 containing tight junctions (TJs) but not adherens junctions, implying involvement of YAP in ZO-1-mediated cell migration. The association of YAP with ZO-1 was mediated by angiomotin (AMOT) because downregulation of AMOT dissociated YAP from ZO-1 and reduced cell migration. E-cadherin restoration in malignant cancer cells induced NF-κB signaling to enhance ZO-1 expression and subsequently stabilize YAP. At high expression levels, YAP associates with ZO-1 via AMOT at TJs, influencing ZO-1-mediated cell migration and maintaining TJ integrity.

KW - Angiomotin

KW - Cell migration

KW - E-cadherin

KW - Tight junction

KW - YAP

KW - ZO-1

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ER -

Yes-associated protein is required for zo-1-mediated tight-junction integrity and cell migration in e-cadherin-restored ags gastric cancer cells

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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