Endothelin-1/endothelin A receptor axis activates RhoA GTPase in epithelial ovarian cancer

Life Sciences
P TocciLaura Rosanò

Abstract

The endothelin-1 (ET-1)/ET A receptor (ETAR) signaling pathway is critical driver of epithelial ovarian cancer (EOC) progression. Emerging evidences demonstrate that the scaffolding protein β-arrestin-1 (β-arr1) downstream of ETAR guides cell motility, although the signaling pathways by which ETAR activation controls these process are not well understood. Here, we set out to molecularly dissect whether RhoA GTPase activation is a mediator of ET-1 signaling controlling EOC cell migration. We cultured EOC cell lines (HEY, SKOV3, OVCAR, A2780 and 2008) with ET-1 and the ET-1R antagonist macitentan. RhoA expression was evaluated by RT-PCR. Activation of RhoA and ROCK1 was evaluated by pull down and kinase assays, respectively. Cell motility was evaluated by chemotaxis and wound healing assays, in untrasfected cells by using ROCK chemical inhibitors, Y-27632 or Fasudil, or in cells after transfection with dominant negative RhoA construct. The phosphorylation of myosin light chain 2 (MLC2) was evaluated by immunoblotting. Pseudopodia formation was evaluated by a pseudopodia kit assay. In EOC cells, ET-1 activates RhoA and downstream ROCK1 and MLC2. These effects were inhibited by β-arr1 silencing, suggesting that ET-1/ETAR regulate R...Continue Reading

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Citations

Jul 31, 2016·Journal of Experimental & Clinical Cancer Research : CR·Laura Rosanò, Anna Bagnato
Aug 5, 2016·International Journal of Molecular Sciences·Qiao ZhangYanjiang Qiao
Jan 30, 2018·Journal of Cellular and Molecular Medicine·Maria Caroline Alves CoelhoMônica R Gadelha
Aug 2, 2017·Expert Opinion on Therapeutic Targets·Laura RosanòAnna Bagnato
Mar 7, 2019·Frontiers in Pharmacology·Anna Bagnato, Laura Rosanò
Jan 31, 2021·Archives of Biochemistry and Biophysics·Yiyuan YangLanfang Li

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