ROCK cooperated with ET-1 to induce epithelial to mesenchymal transition through SLUG in human ovarian cancer cells.
The Rho-associated serine-threonine protein kinase (ROCK) is a downstream effector of Rho GTPases that is frequently activated in the epithelial to mesenchymal transition (EMT) of human ovarian cancer cells. On the other hand, endothelin-1 (ET-1) and its receptor endothelin A receptor (ET(A)R) are overexpressed in primary and metastatic ovarian carcinoma, which suggests that ET-1 promotes tumor dissemination. Hence, two human ovarian carcinoma cell lines, SK-OV-3 and CaOV3, were chosen to study the effects of ET-1/ET(A)R and ROCK in promoting EMT of ovarian cancer cells. We found that ET-1 exposure induced EMT of SK-OV-3 and CaOV3 by monitoring cells morphology, enhanced fibronectin, and reduced E-cadherin protein. At the same time, ET-1/ET(A)R enhanced the level of transcription of SLUG a transcriptional repressor of E-cadherin. More importantly, a constitutively active mutant of ROCK enhanced the transcription of SLUG by stimulating SLUG promoter activity. Furthermore, ROCK inhibitor Y27632 reversed the increase in fibronectin induced by ET-1/ET(A)R. Our data suggest that ROCK cooperated with ET-1/ET(A)R to promote EMT of human ovarian carcinoma cells through upregulation of SLUG mRNA.
Department of Radio-Chemo Therapy, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, China.
Jin
J
Peng
Gong
G
Zhang
Quansheng
Q
Wang
Jianguo
J
Huang
Huan
H
Ma
Yahua
Y
Zhong
Fuxiang
F
Zhou
Conghua
C
Xie
Ali
A
Zhang
D015820:Cadherins / Q000235:genetics; D045744:Cell Line, Tumor; D019332:Endothelin-1 / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044022:Receptor, Endothelin A / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015854:Up-Regulation; D054460:rho-Associated Kinases / Q000378:metabolism*
D015820:Cadherins; D019332:Endothelin-1; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D054460:rho-Associated Kinases