ArticleOncogene2016
Endothelin A receptor drives invadopodia function and cell motility through the β-arrestin/PDZ-RhoGEF pathway in ovarian carcinoma.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The role of MMP-14 in ovarian cancer: a systematic review.Journal of ovarian research · 2021Pooled it
- Organoid modeling identifies EDN1 as a potential oncogenic driver in papillary thyroid carcinoma via modulation of the Hippo-YAP signaling pathway.Journal of endocrinological investigation · 2026Article
- SNX9 Orchestrates Lung Metastasis via EGFR-ERK Signaling and Actin Cytoskeleton Remodeling in Breast Cancer.Oncology research · 2026Article
- YAP signaling orchestrates the endothelin-1-guided invadopodia formation in high-grade serous ovarian cancer.Bioscience reports · 2024Article
- Endothelin-1 receptor blockade impairs invasion patterns in engineered 3D high-grade serous ovarian cancer tumouroids.Clinical science (London, England : 1979) · 2024Article
- Comprehensive evaluation of immunological attributes and immunotherapy responses of positive T cell function regulators in colorectal cancer.BMC gastroenterology · 2024Article
- The β-arrestin1/endothelin axis bolsters ovarian fibroblast-dependent invadosome activity and cancer cell metastatic potential.Cell death & disease · 2024Article
- Endothelin-1 and Its Role in Cancer and Potential Therapeutic Opportunities.Biomedicines · 2024Review
- Oncogenic Gαq activates RhoJ through PDZ-RhoGEF.International journal of molecular sciences · 2023Article
- The interaction of β-arrestin1 with talin1 driven by endothelin A receptor as a feature of α5β1 integrin activation in high-grade serous ovarian cancer.Cell death & disease · 2023Article
- Comprehensive analysis of the prognostic implications and functional exploration of PAK gene family in human cancer.Cancer cell international · 2022Article
- Article
- Amoeboid migration in health and disease: Immune responsesFrontiers in cell and developmental biology · 2022Review
- Rho-Kinase as a Target for Cancer Therapy and Its Immunotherapeutic Potential.International journal of molecular sciences · 2021Review
- Role of RhoC in cancer cell migration.Cancer cell international · 2021Review
- Inhibition of LIM kinase reduces contraction and proliferation in bladder smooth muscle.Acta pharmaceutica Sinica. B · 2021Article
- YAP and endothelin-1 signaling: an emerging alliance in cancer.Journal of experimental & clinical cancer research : CR · 2021Review
- Ovarian Cancer-Driven Mesothelial-to-Mesenchymal Transition is Triggered by the Endothelin-1/β-arr1 Axis.Frontiers in cell and developmental biology · 2021Article
- Article
- Tumor Cellular and Microenvironmental Cues Controlling Invadopodia Formation.Frontiers in cell and developmental biology · 2020Review
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The endothelin-1 (ET-1)/ET A receptor (ETAR) signalling pathway is a well-established driver of epithelial ovarian cancer (EOC) progression. One key process promoted by ET-1 is tumor cell invasion, which requires the scaffolding functions of β-arrestin-1 (β-arr1) downstream of the receptor; however, the potential role of ET-1 in inducing invadopodia, which are crucial for cellular invasion and tumor metastasis, is completely unknown. We describe here that ET-1/ETAR, through β-arr1, activates RhoA and RhoC GTPase and downstream ROCK (Rho-associated coiled coil-forming kinase) kinase activity, promoting actin-based dynamic remodelling and enhanced cell invasion. This is accomplished by the direct interaction of β-arr1 with PDZ-RhoGEF (postsynaptic density protein 95/disc-large/zonula occludens-RhoGEF). Interestingly, ETAR-mediated invasive properties are related to the regulation of invadopodia, as evaluated by colocalization of actin with cortactin, as well as with TKS5 and MT1-MMP (membrane type 1-matrix metalloproteinase) with areas of matrix degradation, and activation of cofilin pathway, which is crucial for regulating invadopodia activity. Depletion of PDZ-RhoGEF, or β-arr1, or RhoC, as well as the treatment with the dual ET-1 receptor antagonist macitentan, significantly impairs invadopodia function, MMP activity and invasion, demonstrating that β-arr1/PDZ-RhoGEF interaction mediates ETAR-driven ROCK-LIMK-cofilin pathway through the control of RhoC activity. In vivo, macitentan is able to inhibit metastatic dissemination and cofilin phosphorylation. Collectively, our data unveil a noncanonical activation of the RhoC/ROCK pathway through the β-arr1/PDZ-RhoGEF complex as a regulator of ETAR-induced motility and metastasis, establishing ET-1 axis as a novel regulator of invadopodia protrusions through the RhoC/ROCK/LIMK/cofilin pathway during the initial steps of EOC invasion.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.