ArticleCellular signalling2014
Endothelin-1/endothelin A receptor-mediated biased signaling is a new player in modulating human ovarian cancer cell tumorigenesis.
Article in Cellular signalling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- DNA damaging agents boost the transcription of endothelin A receptor in high-grade serous ovarian cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- Endothelin-3 is epigenetically silenced in endometrioid endometrial cancer.Journal of cancer research and clinical oncology · 2023Article
- Review
- A human antibody against human endothelin receptor type A that exhibits antitumor potency.Experimental & molecular medicine · 2021Article
- Ambrisentan, an endothelin receptor type A-selective antagonist, inhibits cancer cell migration, invasion, and metastasis.Scientific reports · 2020Article
- Phenotypic assessment and ligand screening of ETA/ETB receptors with label-free dynamic mass redistribution assay.Naunyn-Schmiedeberg's archives of pharmacology · 2020Article
- Novel treatment avenues for uterine leiomyoma: a new implication for endothelin?Clinical science (London, England : 1979) · 2018Article
- β-arrestin-biased agonism of β-adrenergic receptor regulates Dicer-mediated microRNA maturation to promote cardioprotective signaling.Journal of molecular and cellular cardiology · 2018Article
- Endothelin Promotes Colorectal Tumorigenesis by Activating YAP/TAZ.Cancer research · 2017Article
- Biased G Protein-Coupled Receptor Signaling: New Player in Modulating Physiology and Pathology.Biomolecules & therapeutics · 2017Review
- Evidence for biased agonists and antagonists at the endothelin receptors.Life sciences · 2016Review
- β-arrestin1 at the cross-road of endothelin-1 signaling in cancer.Journal of experimental & clinical cancer research : CR · 2016Review
- Nuclear β-arrestin1 is a critical cofactor of hypoxia-inducible factor-1α signaling in endothelin-1-induced ovarian tumor progression.Oncotarget · 2016Article
- Activation of ETA Receptor by Endothelin-1 Induces Hepatocellular Carcinoma Cell Migration and Invasion via ERK1/2 and AKT Signaling Pathways.The Journal of membrane biology · 2016Article
- Endothelin.Pharmacological reviews · 2016Review
- Discovery of Dual ETA/ETB Receptor Antagonists from Traditional Chinese Herbs through in Silico and in Vitro Screening.International journal of molecular sciences · 2016Article
- Endothelin therapeutics in cancer: Where are we?American journal of physiology. Regulatory, integrative and comparative physiology · 2016Review
- Identification of gene signatures regulated by carvedilol in mouse heart.Physiological genomics · 2015Article
- Disrupting the endothelin and Wnt relationship to overcome chemoresistance.Molecular & cellular oncologyArticle
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The endothelin-1 (ET-1)/endothelin A receptor (ETAR, a G protein-coupled receptor) axis confers pleiotropic effects on both tumor cells and the tumor microenvironment, modulating chemo-resistance and other tumor-associated processes by activating Gαq- and β-arrestin-mediated pathways. While the precise mechanisms by which these effects occur remain to be elucidated, interference with ETAR signaling has emerged as a promising antitumor strategy in many cancers including ovarian cancer (OC). However, current clinical approaches using ETAR antagonists in the absence of a detailed knowledge of downstream signaling have resulted in multiple adverse side effects and limited therapeutic efficacy. To maximize the safety and efficacy of ETAR-targeted OC therapy, we investigated the role of other G protein subunits such as Gαs in the ETAR-mediated ovarian oncogenic signaling. In HEY (human metastatic OC) cells where the ET-1/ETAR axis is well-characterized, Gαs signaling inhibits ETAR-mediated OC cell migration, wound healing, proliferation and colony formation on soft agar while inducing OC cell apoptosis. Mechanistically, ET-1/ETAR is coupled to Gαs/cAMP signaling in the same ovarian carcinoma-derived cell line. Gαs/cAMP/PKA activation inhibits ETAR-mediated β-arrestin activation of angiogenic/metastatic Calcrl and Icam2 expression. Consistent with our findings, Gαs overexpression is associated with improved survival in OC patients in the analysis of the Cancer Genome Atlas data. In conclusion, our results indicate a novel function for Gαs signaling in ET-1/ETAR-mediated OC oncogenesis and may provide a rationale for a biased signaling mechanism, which selectively activates Gαs-coupled tumor suppressive pathways while blocking Gαq-/β-arrestin-mediated oncogenic pathways, to improve the targeting of the ETAR axis in OC.
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