ArticleOncotarget2016
Nuclear β-arrestin1 is a critical cofactor of hypoxia-inducible factor-1α signaling in endothelin-1-induced ovarian tumor progression.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 30 citations in OpenAlex.
- The extracellular matrix protein type I collagen and fibronectin are regulated by β-arrestin-1/endothelin axis in human ovarian fibroblasts.Journal of experimental & clinical cancer research : CR · 2025Article
- Bevacizumab in ovarian cancer therapy: current advances, clinical challenges, and emerging strategies.Frontiers in bioengineering and biotechnology · 2025Review
- Targeting tumor-stroma communication by blocking endothelin-1 receptors sensitizes high-grade serous ovarian cancer to PARP inhibition.Cell death & disease · 2023Article
- Radiomics signature: A potential biomarker for β-arrestin1 phosphorylation prediction in hepatocellular carcinoma.World journal of gastroenterology · 2022Article
- YAP and endothelin-1 signaling: an emerging alliance in cancer.Journal of experimental & clinical cancer research : CR · 2021Review
- A GSK3-SRF Axis Mediates Angiotensin II Induced Endothelin Transcription in Vascular Endothelial Cells.Frontiers in cell and developmental biology · 2021Article
- The Emerging Role of Adhesion GPCRs in Cancer.ACS pharmacology & translational science · 2020Review
- Targeting the Endothelin-1 Receptors Curtails Tumor Growth and Angiogenesis in Multiple Myeloma.Frontiers in oncology · 2020Article
- β-arrestin1/YAP/mutant p53 complexes orchestrate the endothelin A receptor signaling in high-grade serous ovarian cancer.Nature communications · 2019Article
- Targeting Endothelin-1 Receptor/β-Arrestin-1 Axis in Ovarian Cancer: From Basic Research to a Therapeutic Approach.Frontiers in endocrinology · 2019Review
- New Routes in GPCR/β-Arrestin-Driven Signaling in Cancer Progression and Metastasis.Frontiers in pharmacology · 2019Review
- The role of hypoxic signalling in metastasis: towards translating knowledge of basic biology into novel anti-tumour strategies.Clinical & experimental metastasis · 2018Review
- hMENA is a key regulator in endothelin-1/β-arrestin1-induced invadopodial function and metastatic process.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Investigation of hypoxia networks in ovarian cancer via bioinformatics analysis.Journal of ovarian research · 2018Article
- Hypoxia Inducible Factor (HIF) Hydroxylases as Regulators of Intestinal Epithelial Barrier Function.Cellular and molecular gastroenterology and hepatology · 2017Review
- Hepatitis B virus X induces inflammation and cancer in mice liver through dysregulation of cytoskeletal remodeling and lipid metabolism.Oncotarget · 2016Article
- β-arrestin1 at the cross-road of endothelin-1 signaling in cancer.Journal of experimental & clinical cancer research : CR · 2016Review
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia-inducible factor-1α (HIF-1α) mediates the response to hypoxia or other stimuli, such as growth factors, including endothelin-1 (ET-1), to promote malignant progression in numerous tumors. The importance of cofactors that regulate HIF-1α signalling within tumor is not well understood. Here we elucidate that ET-1/ET(A) receptor (ET(A)R)-induced pathway physically and functionally couples the scaffold protein β-arrestin1 (β-arr1) to HIF-1α signalling. In epithelial ovarian cancer (EOC) cells, ET-1/ET(A)R axis induced vascular-endothelial growth factor (VEGF) expression through HIF-1α nuclear accumulation. In these cells, activation of ET(A)R by ET-1, by mimicking hypoxia, promoted the nuclear interaction between β-arr1 and HIF-1α and the recruitment of p300 acetyltransferase to hypoxia response elements on the target gene promoters, resulting in enhanced histone acetylation, and HIF-1α target gene transcription. Indeed, β-arr1-HIF-1α interaction regulated the enhanced expression and release of downstream targets, such as ET-1 and VEGF, required for tumor cell invasion and pro-angiogenic effects in endothelial cells. These effects were abrogated by β-arr1 or HIF-1α silencing or by pharmacological treatment with the dual ET-1 receptor antagonist macitentan. Interestingly, ET(A)R/β-arr1 promoted the self-amplifying HIF-1α-mediated transcription of ET-1 that sustained a regulatory circuit involved in invasive and angiogenic behaviors. In a murine orthotopic model of metastatic human EOC, treatment with macitentan, or silencing of β-arr1, inhibits intravasation and metastasis formation. Collectively, these findings reveal the interplay of β-arr1 with HIF-1α in the complexity of ET-1/ET(A)R signalling, mediating epigenetic modifications directly involved in the metastatic process, and suggest that targeting ET-1-dependent β-arr1/HIF-1α pathway by using macitentan may impair EOC progression.
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