TAZ Mediates Lysophosphatidic Acid-Induced Migration and Proliferation of Epithelial Ovarian Cancer Cells
Background: Transcriptional co-activator with PDZ-binding motif (TAZ), a downstream effector of the Hippo pathway, has been reported to regulate organ size, tissue homeostasis, and tumorigenesis by acting as a transcriptional co-activator. Lysophosphatidic acid (LPA) is a bioactive lipid implicated...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Cell Physiol Biochem Press GmbH & Co KG
2013-07-01
|
Series: | Cellular Physiology and Biochemistry |
Subjects: | |
Online Access: | http://www.karger.com/Article/FullText/354434 |
id |
doaj-cc5be5acce914749b2f14feebcce32d9 |
---|---|
record_format |
Article |
spelling |
doaj-cc5be5acce914749b2f14feebcce32d92020-11-24T21:44:31ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782013-07-0132225326310.1159/000354434354434TAZ Mediates Lysophosphatidic Acid-Induced Migration and Proliferation of Epithelial Ovarian Cancer CellsGeun Ok JeongSang Hun ShinEun Jin SeoYang Woo KwonSoon Chul HeoKi-Hyung KimMan-Soo YoonDong-Soo SuhJae Ho KimBackground: Transcriptional co-activator with PDZ-binding motif (TAZ), a downstream effector of the Hippo pathway, has been reported to regulate organ size, tissue homeostasis, and tumorigenesis by acting as a transcriptional co-activator. Lysophosphatidic acid (LPA) is a bioactive lipid implicated in tumorigenesis and metastasis of ovarian cancer through activation of G protein-coupled receptors. However, the involvement of TAZ in LPA-induced tumorigenesis of ovarian cancer has not been elucidated. Methods: In order to demonstrate the role of TAZ in LPA-stimulated tumorigenesis, the effects of LPA on TAZ expression and cell migration were determined by Western blotting and chemotaxis analyses in R182 human epithelial ovarian cancer cells. Results and Conclusion: Treatment of R182 cells with the LPA receptor inhibitor Ki16425 blocked LPA-induced cell migration. In addition, transfection of R182 cells with small interfering RNA specific for LPA receptor 1 resulted in abrogation of LPA-stimulated cell migration. LPA induced phosphorylation of ERK and p38 MAP kinase in R182 cells and pretreatment of cells with the MEK-ERK pathway inhibitor U0126, but not the p38 MAPK inhibitor SB202190, resulted in abrogation of LPA-induced cell migration. Pretreatment of R182 cells with U0126 attenuated LPA-induced mRNA levels of TAZ and its transcriptional target genes, such as CTGF and CYR61, without affecting phosphorylation level of YAP. These results suggest that MEK-ERK pathway plays a key role in LPA-induced cell migration and mRNA expression of TAZ in R182 cells, without affecting stability of TAZ protein. In addition, small interfering RNA-mediated silencing of TAZ expression attenuated LPA-stimulated migration of R182 cells. These results suggest that TAZ plays a key role in LPA-stimulated migration of epithelial ovarian cancer cells.http://www.karger.com/Article/FullText/354434Lysophosphatidic acidTAZOvarian cancerMigrationProliferation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Geun Ok Jeong Sang Hun Shin Eun Jin Seo Yang Woo Kwon Soon Chul Heo Ki-Hyung Kim Man-Soo Yoon Dong-Soo Suh Jae Ho Kim |
spellingShingle |
Geun Ok Jeong Sang Hun Shin Eun Jin Seo Yang Woo Kwon Soon Chul Heo Ki-Hyung Kim Man-Soo Yoon Dong-Soo Suh Jae Ho Kim TAZ Mediates Lysophosphatidic Acid-Induced Migration and Proliferation of Epithelial Ovarian Cancer Cells Cellular Physiology and Biochemistry Lysophosphatidic acid TAZ Ovarian cancer Migration Proliferation |
author_facet |
Geun Ok Jeong Sang Hun Shin Eun Jin Seo Yang Woo Kwon Soon Chul Heo Ki-Hyung Kim Man-Soo Yoon Dong-Soo Suh Jae Ho Kim |
author_sort |
Geun Ok Jeong |
title |
TAZ Mediates Lysophosphatidic Acid-Induced Migration and Proliferation of Epithelial Ovarian Cancer Cells |
title_short |
TAZ Mediates Lysophosphatidic Acid-Induced Migration and Proliferation of Epithelial Ovarian Cancer Cells |
title_full |
TAZ Mediates Lysophosphatidic Acid-Induced Migration and Proliferation of Epithelial Ovarian Cancer Cells |
title_fullStr |
TAZ Mediates Lysophosphatidic Acid-Induced Migration and Proliferation of Epithelial Ovarian Cancer Cells |
title_full_unstemmed |
TAZ Mediates Lysophosphatidic Acid-Induced Migration and Proliferation of Epithelial Ovarian Cancer Cells |
title_sort |
taz mediates lysophosphatidic acid-induced migration and proliferation of epithelial ovarian cancer cells |
publisher |
Cell Physiol Biochem Press GmbH & Co KG |
series |
Cellular Physiology and Biochemistry |
issn |
1015-8987 1421-9778 |
publishDate |
2013-07-01 |
description |
Background: Transcriptional co-activator with PDZ-binding motif (TAZ), a downstream effector of the Hippo pathway, has been reported to regulate organ size, tissue homeostasis, and tumorigenesis by acting as a transcriptional co-activator. Lysophosphatidic acid (LPA) is a bioactive lipid implicated in tumorigenesis and metastasis of ovarian cancer through activation of G protein-coupled receptors. However, the involvement of TAZ in LPA-induced tumorigenesis of ovarian cancer has not been elucidated. Methods: In order to demonstrate the role of TAZ in LPA-stimulated tumorigenesis, the effects of LPA on TAZ expression and cell migration were determined by Western blotting and chemotaxis analyses in R182 human epithelial ovarian cancer cells. Results and Conclusion: Treatment of R182 cells with the LPA receptor inhibitor Ki16425 blocked LPA-induced cell migration. In addition, transfection of R182 cells with small interfering RNA specific for LPA receptor 1 resulted in abrogation of LPA-stimulated cell migration. LPA induced phosphorylation of ERK and p38 MAP kinase in R182 cells and pretreatment of cells with the MEK-ERK pathway inhibitor U0126, but not the p38 MAPK inhibitor SB202190, resulted in abrogation of LPA-induced cell migration. Pretreatment of R182 cells with U0126 attenuated LPA-induced mRNA levels of TAZ and its transcriptional target genes, such as CTGF and CYR61, without affecting phosphorylation level of YAP. These results suggest that MEK-ERK pathway plays a key role in LPA-induced cell migration and mRNA expression of TAZ in R182 cells, without affecting stability of TAZ protein. In addition, small interfering RNA-mediated silencing of TAZ expression attenuated LPA-stimulated migration of R182 cells. These results suggest that TAZ plays a key role in LPA-stimulated migration of epithelial ovarian cancer cells. |
topic |
Lysophosphatidic acid TAZ Ovarian cancer Migration Proliferation |
url |
http://www.karger.com/Article/FullText/354434 |
work_keys_str_mv |
AT geunokjeong tazmediateslysophosphatidicacidinducedmigrationandproliferationofepithelialovariancancercells AT sanghunshin tazmediateslysophosphatidicacidinducedmigrationandproliferationofepithelialovariancancercells AT eunjinseo tazmediateslysophosphatidicacidinducedmigrationandproliferationofepithelialovariancancercells AT yangwookwon tazmediateslysophosphatidicacidinducedmigrationandproliferationofepithelialovariancancercells AT soonchulheo tazmediateslysophosphatidicacidinducedmigrationandproliferationofepithelialovariancancercells AT kihyungkim tazmediateslysophosphatidicacidinducedmigrationandproliferationofepithelialovariancancercells AT mansooyoon tazmediateslysophosphatidicacidinducedmigrationandproliferationofepithelialovariancancercells AT dongsoosuh tazmediateslysophosphatidicacidinducedmigrationandproliferationofepithelialovariancancercells AT jaehokim tazmediateslysophosphatidicacidinducedmigrationandproliferationofepithelialovariancancercells |
_version_ |
1725909687955619840 |